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1

Ostertag, Luisa Martha. "The impact of dietary polyphenols on human platelets : integrating functional and nutrigenomic analyses." Thesis, University of Aberdeen, 2011. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=185749.

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This thesis aims to integrate functional and nutrigenomics analyses to examine how dietary polyphenols affect human platelet function and thus may contribute to the prevention of cardiovascular diseases. Initially, 26 low molecular weight phenolic compounds were screened for their effects on platelet aggregation and P-selectin expression in vitro. Only high, non-physiological concentrations of some phenolics showed anti-platelet effects. In parallel we conducted a systematic review of the literature to assess how polyphenol-rich foodstuffs, beverages, or extracts affect platelet function in humans. Cocoa-derived flavan-3-ols were the only class of dietary polyphenols that consistently showed anti-platelet effects in both, acute and chronic settings. Consequently we conducted an acute randomised-controlled human intervention study in which healthy volunteers consumed three different types of chocolates containing different amounts of flavan-3-ols. We found that flavan-3-ol-enriched dark chocolate beneficially affected ex vivo bleeding time, platelet aggregation and P-selectin expression. These effects were gender-dependent. Bioavailability of cocoa-derived flavan-3-ols, as assessed by a targeted metabolomics approach, was also gender-dependent. Using a platelet proteomics approach, we found subtle changes in platelet protein levels 2 h after consumption of flavan-3-ol-enriched chocolate in men, which may partly explain the observed anti-platelet effects. Finally, we assessed whether flavan-3-ols are internalised in platelets after consumption of dark chocolate. No internalisation could be found up to 2.5 h after chocolate ingestion, despite these compounds appearing in plasma. In conclusion, flavan- 3-ol-enriched dark chocolate beneficially affects platelet function in a gender-dependent way, but underpinning mechanisms are still unknown. Furthermore, current insights into their bioavailability cannot fully explain the ability of flavan-3-ols to affect platelet function. Successful future progress of research into the bioavailability and mechanisms of flavan-3- ols in vitro and in vivo will depend on the availability of pure standards for the major human metabolites of flavan-3-ols.
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2

Sánchez, González Claudia Alejandra. "Nutrigenomic approach to study the potential role of walnut polyphenols and their human metabolites in cancer prevention and treatment." Doctoral thesis, Universitat de Barcelona, 2015. http://hdl.handle.net/10803/315837.

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Epidemiologic studies and clinical trials have demonstrated consistent benefits of walnut (Juglans regia L.) consumption. Walnuts have been described as a rich source of polyphenols with a broad array of different structures. However, an accurate screening of its complete phenolic profile was lacking. Using liquid chromatography coupled with electrospray ionization hybrid linear trap quadrupole-Orbitrap mass spectrometry (LC–LTQ-Orbitrap) a comprehensive identification of phenolic compounds in walnuts was performed. A total of 120 compounds were identified, with ellagitannins, ellagic acid and its derivatives, as major polyphenols in walnuts. After consumption, ellagitannins are hydrolyzed to release ellagic acid, which is converted by gut microflora to urolithin A (UA) and urolithin B (UB). Ellagitannins and their metabolites have been shown to slow down cancer development and progression. The identification of dietary agents that may modulate molecular pathways related to cancer is of great interest. Therefore, the main aim of this study was to determine gene expression changes induced by urolithins using a nutrigenomic approach. We investigated the effects of urolithins on the expression of prostate specific antigen and the androgen receptor in a prostate cancer cell model. The mRNA and protein levels of both prostate specific antigen and androgen receptor were down-regulated after incubating LNCaP cells with urolithins A and B. Transient transfection of PC-3 cells with a luciferase construct driven by the PSA-promoter containing three androgen response elements showed that urolithins inhibited AR-mediated PSA expression at the transcriptional level. Electrophoretic Mobility Shift Assays revealed that urolithins decreased the androgen receptor binding to its consensus Response Element. In addition, we performed a genomic analysis to study the effect of UA on whole genome expression in LNCaP cells. CDKN1A, a node gene determined by Biological Association Networks (BANs) using the list of differentially expressed genes, was further validated; its promoter activity, mRNA and protein levels were significantly up-regulated. The role urolithins have in the modulation of the cell cycle and apoptosis induction was also explored. Cell cycle was measured by flow cytometry, and apoptosis was determined by caspase 3/7 activation and using the rhodamine method. Cell cycle analyses showed an increase at G1, we also observed an induction of apoptosis and caspase 3/7 activation and this effect correlated with a decrease in the anti-apoptotic protein Bcl-2. Our results suggest that urolithins A and B attenuate the function of the AR by repressing its expression. A down-regulation of AR and PSA mRNA and protein levels could provoke an interruption of the interaction between PSA and AR, with a proven role in prostate cancer development and progression. In addition a clear effect of urolithin A on whole genome expression in a prostate cancer cell model was observed. The significant up regulation of p21, which has a known role in cell cycle and apoptosis, correlated with an increased percentage of cells in the G1 phase of the cell cycle, furthermore, the multi-targeted effects of urolithins resulted in an induction of apoptosis. The aforementioned results indicate a potential role of walnuts as a chemo-preventive and/or chemo-therapeutic agent for prostate cancer.
Estudios clínicos y epidemiológicos han demostrado que existen múltiples beneficios sobre la salud por incluir nueces (Juglans regia L.) en la dieta. Existe una amplia evidencia de la relación de la dieta y componentes específicos de nuestros alimentos con vías moleculares importantes en el desarrollo del cáncer. La etiología del cáncer es multifactorial, una variedad de factores genéticos, dietéticos y de estilo de vida juegan un rol fundamental en el desarrollo y progresión de esta enfermedad. La identificación de los mecanismos moleculares involucrados en la carcinogénesis y su relación con factores de riesgo modificables genera una base para el desarrollo de estrategias específicas de prevención. La nutrigenómica es un enfoque nuevo en la nutrición que busca explorar la interacción gen-dieta y el posible papel que esta interacción juega en el desarrollo de enfermedades. Utilizando una aproximación nutrigenómica, el objetivo de esta tesis doctoral es analizar el efecto de las urolitinas A y B, metabolitos del polifenol mayoritario en nueces, sobre vías moleculares clave en el desarrollo y progresión del cáncer de próstata. Nuestros resultados sugieren que las urolitinas A y B atenúan la función del receptor de andrógeno al inhibir su expresión. La disminución de los niveles de mRNA y proteína del receptor de andrógeno y su diana el antígeno prostático especifico podría causar una interrupción en la interacción entre ambas proteínas, las cuales se sabe juegan un papel en el desarrollo y progresión del cáncer de próstata. Además, a través de un estudio genómico funcional se pudo comprobar el claro efecto que ejerce la urolitina A sobre la expresión génica en un modelo de cáncer de próstata. La urolitina A causó una sobrexpresión de p21, proteína reguladora del ciclo celular, lo cual se correlacionó a un aumento en el porcentaje de células en la fase G1 del ciclo celular. Asimismo, el efecto de las urolitinas sobre múltiples dianas, incluyendo Bcl-2, caspasas 3 y 7 y p21, resultaron en la inducción de apoptosis. En resumen, el estudio de la relación entre dieta y cáncer a través de la aplicación de nuevas tecnologías ligadas a enfoques novedosos como la nutrigenómica podría permitir desarrollar recomendaciones y estrategias de prevención efectivas.
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Frahnow, Turid [Verfasser], and Matthias Bernd [Akademischer Betreuer] Schulze. "Bioinformatische Analyse der NUGAT-Studie (NUtriGenomic Analysis in Twins) : Verfahren zur Integration lipidomischer, transkriptomischer und metabolischer Daten / Turid Frahnow ; Betreuer: Matthias Bernd Schulze." Potsdam : Universität Potsdam, 2016. http://d-nb.info/121840194X/34.

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4

Joumard-Cubizolles, Laurie. "Propriétés anti-athérogènes du DHA : effets nutrigénomiques au niveau aortique et rôle potentiel des métabolites issus de la peroxydation." Thesis, Clermont-Ferrand 1, 2013. http://www.theses.fr/2013CLF1MM17.

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Les acides gras polyinsaturés oméga-3 à longue chaîne (AGPIω3-LC), principalement représentés par l'acide eicosapentaénoïque (EPA) et l'acide docosahexaénoïque (DHA), présentent des effets bénéfiques vis-à-vis de l'athérosclérose. Leur action au niveau vasculaire est suggérée. Les mécanismes d'action sont mal compris du fait de la complexité d'action des AGPIω3-LC au niveau cellulaire. Les AGPIω3-LC affectent de nombreuses protéines y compris les facteurs de transcription, ce qui engendre la modulation de l'expression de nombreux gènes. La complexité s'accroît si l'on considère l'ensemble des métabolites oxygénés issus des AGPIω3-LC. Les métabolites issus de la peroxydation lipidique peuvent être produits en abondance au cours de l'athérogenèse mais leur bioactivité est quasiment inconnue. Des points majeurs restent à éclaircir comme l'identification des cibles cellulaires et moléculaires au niveau vasculaire et la bioactivité des métabolites peroxydés. Objectifs : étudier l'impact du DHA au niveau vasculaire et évaluer la bioactivité de certains métabolites issus de la peroxydation lipidique du DHA. Les travaux visant à étudier les propriétés athéro-protectrices du DHA n'ont jusqu'à présent pas permis d'obtenir une vision globale de son spectre d'action. La nutrigénomique a paru être une approche pertinente pour étudier les effets du DHA au niveau vasculaire. Une étude in vivo a été réalisée sur des souris athérosclérotiques LDLR-/- recevant ou non une supplémentation en DHA (2% de l'apport énergétique journalier). Le rôle athéro-protecteur du DHA a été confirmé dans une étude précédente rapportant une diminution de 35% de l'étendue des lésions au niveau aortique dans le groupe DHA. Au niveau protéique, nous avons montré une altération significative de l'expression de protéines intervenant principalement au niveau des métabolismes glucidique et lipidique mais aussi dans les défenses anti-oxydantes. Au niveau génique, la composante inflammatoire s'est avérée être une cible majeure du DHA au niveau vasculaire. La supplémentation en DHA a réduit l'expression de gènes impliqués dans l'adhésion cellulaire, la chimiotaxie et la présentation de l'antigène. Plusieurs gènes se sont avérés être des marqueurs phénotypiques des macrophages et l'analyse des régulateurs transcriptionnels montrait une implication probable de PPARγ, IFNγ et NFκB dans les modulations d'expression génique observées. Nos analyses suggèrent une orientation préférentielle des macrophages vers un phénotype réparateur de type M2 chez les souris recevant la supplémentation en DHA. Une analyse immunohistochimique au niveau aortique a révélé une plus grande abondance d'arginase I. Une approche plus ciblée alliant une étude in vitro sur un modèle de macrophages humains et l'utilisation de métabolites peroxydés spécifiques du DHA, les neuroprostanes, nous a permis de conforter notre hypothèse selon laquelle le DHA pourrait agir au moins en partie via ses métabolites peroxydés. L'exposition des macrophages à deux types de neuroprostanes (les 4-F4t et les 14-A4-Neuroprostanes) a permis de réduire significativement l'expression et la sécrétion de plusieurs médiateurs pro-inflammatoires. Des résultats préliminaires suggèrent que ces effets anti-inflammatoires des neuroprostanes seraient indépendants de PPARγ mais liés à une inhibition de la voie NFκB. L'étude in vivo et l'utilisation de la nutrigénomique nous ont permis d'explorer de façon ouverte et non biaisée l'impact du DHA au niveau vasculaire. Les résultats sont que le DHA active le métabolisme énergétique et les défenses anti-oxydantes et diminue l'état inflammatoire avec une implication probable du DHA dans l'orientation phénotypique des macrophages vers un phénotype réparateur de type M2. Les résultats obtenus in vitro sur macrophages primaires humains confirment que les métabolites peroxydés du DHA contribuent à ses propriétés anti-inflammatoires
Numerous studies have reported beneficial effects of long chain omega-3 polyunsaturated fatty acids (LC-ω3PUFAs) on atherosclerosis and associated cardiovascular events. These fatty acids are mainly represented by eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). LC-ω3PUFAs exert their athero-protective action mainly by a reduction of triglyceridemia, increased endothelial relaxation, and reduced inflammation. Their specific action at the vascular level is suggested. Their mechanisms of action are still only partially understood because of the complexity of action of LC-ω3PUFAs at the cellular level. LC-ω3PUFAs affect several membrane or cytosolic proteins, including transcription factors, which modulate numerous gene expression. The complexity is further increased when considering a wide range of oxygenated metabolites derived from LC-ω3PUFAs. Among them, the metabolites from lipid peroxidation may be produced in abundance during atherogenesis but their bioactivity is almost unknown. There are still major issues to be clarified, such as the identification of cellular and molecular targets at the vascular level ; the bioactivity of peroxidized metabolites that could play a key role in the prevention of atherosclerosis. The objective of this work was to study the impact of DHA at the vascular level and to evaluate the bioactivity of selected metabolites from DHA lipid peroxidation. Studies on anti-atherogenic properties of DHA have so far been carried out only in a targeted manner that does not provide a comprehensive and integrated view of its spectrum of action. Nutrigenomics appears to be a relevant approach to study the effects of DHA at the vascular level. In vivo study was performed on LDLR-/- atherosclerotic mice supplemented or not with DHA. The athero-protective effect of DHA has been confirmed in the previous study performed by our team reporting a 35% decrease of the atherosclerotic lesion in the DHA group. Aorta proteome study demonstrated a significant alteration of the expression of proteins involved mainly in the carbohydrate and lipid metabolism and also in antioxidant defenses. At the transcriptome level, the inflammatory component of atherosclerosis appears to be a major target of DHA at the vascular level. More precisely, DHA supplementation reduced the expression of genes involved in cell adhesion, chemotaxis and antigen presentation. Several genes were found to be phenotypic markers of macrophages and analysis of transcriptional regulators showed a possible contribution of PPARγ, IFNγ and NFκB to the observed modulation of gene expression. Our results suggest a preferential orientation of macrophages to a M2 type repair phenotype in mice receiving DHA supplementation. This was confirmed by immunohistochemical analysis at the aorta which revealed a greater abundance of arginase I. We chose a focused in vitro study of the action of specific DHA peroxidized metabolites: the neuroprostanes on a human macrophages. This study allowed us to confirm our hypothesis that DHA may act at least in part via its peroxidized metabolites. The macrophages exposition to 2 types of neuroprostanes (4-F4t and 14-A4-Neuroprostanes) has significantly reduced the expression and secretion of several pro-inflammatory mediators. Preliminary results suggest that these anti-inflammatory effects are PPARγ-independent but related to inhibition of NFκB pathway. In vivo study, and nutrigenomics approach, allowed us to explore the impact of DHA at the vascular level by an open and unbiased way. The results are that DHA activates energy metabolism and antioxidant defenses and reduces the inflammatory component of atherosclerosis with a possible involvement of DHA in the phenotypic direction of macrophages to a M2 type repair phenotype. The results obtained in vitro on primary human macrophages confirmed that DHA peroxidized metabolites contribute to its anti-inflammatory properties
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Tacchi, Luca. "Molecular basis of improved feeds for aquaculture : a nutrigenomics approach." Thesis, University of Aberdeen, 2011. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=179562.

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The growth of aquaculture industry, and in particular of salmonids, has dramatically increased in the last decades to supply the growing worldwide demand for fish products. The expansion of aquaculture needs a good management to ensure the sustainability of this activity. In particular, improving feeds for aquaculture to enhance health and performance of reared fish is imperative for this industry. Molecular biological approacches can help interpret responses to new diets and immune responses. Ubiquitin ligases (UbE3s) play a pivotal role in the ubiquitin proteasome pathway of protein degradation and are markers that could be linked to health and performance of fish. Six UbE3s were characterized, 4 are related to muscle catabolism and two involved in NF-kB activation. Atrogin-1 and MuRF genes were increased following food deprivation and a proinflammatory stimulation. MULAN and Mul1b, are mitochondrial activators of NF-kB and the expression of both genes was increased following a proinflammatory immune challenge both in vivo and in vitro. These genes have been used as markers in dietary traits to understand responses. A transcriptome study using Atlantic salmon fed a commercially available functional feed designed for optimal health status compared to a standard feed was performed. Both the liver and muscle were chosen for the transcriptomic analysis. In liver, a number of process were found down regulated, including protein turnover and innate immunity. No significant alterations were found in muscle. To determine the effect of a high plant protein diet (PP), compared to a marine profile diet (MP) in Atlantic a transcriptomic analysis was performed. Fish grew equally well on both diets and no significant histological differences were seen in intestine. The PP diet induced tissue specific changes in gene expression, with the mid intestine showing activation of the adaptive immune response and protein turnover. In liver cell proliferation and apoptosis indicate cellular reorganization and also a general suppression of processes such as immune response was observed. In contrast muscle tissue showed reduced protein metabolism and decrease in immune gene expression suggesting less energy expenditure in this tissue. To assess fish response to Piscirickttsia salmonis, the etiological agent of the salmonid rickettsial seeticemia (SRS), a transcriptomic analysis was carried out. P. salmonis infection has profound effects on transcription in the head kidney, liver and muscle of salmon. Head kidney, liver and muscle tissue showed a decrease in expression of mRNAs related to acquired immune function indicating the pathogen is down regulating this response controlled in part by the inhibition of the G-protein signalling pathway, whereas the innate immune response was increased in head kidney. Liver and muscle also responded, including specific responses in each tissue type. These results improve understanding of the mechanisms by which this bacterium survives and replicates within host cells and may assist selection of molecular biomarkers useful for the development of a diagnostic tools, vaccines and therapeutants for the aquaculture industry. Using markers selected from the previous experiments, the effect of four different diets, a marine profile diet (MP/FO), a plant protein diet (PP/FO), a vegetable oil diet (MP/VO) and PP/VO diet, in Atlantic salmon were examined. Markers for protein and lipid metabolism and immune response were studied in mid intestine, liver and muscle of fish fed for 77 days the four diets. Small but significant changes were observed, but despite of this, fish fed all the four diets showed similar growth rates. Moreover, to study the possible effect of the diets on fish health, the expression of specific SRS markers was studied in head kidney and liver of fish fed the four diets and infected with P. salmonis. The SRS challenge demonstrated that all groups of fish were able to respond efficiently to the pathogen. In conclusion, these new diets may represent good alternatives to fish meal (FM) and fish oil (FO) diets indicating that a replacement of marine diets with vegetable sources is possible in Atlantic salmon without affecting neither fish growth and performance nor the health of fish. The findings presented in this thesis suggest that E3 ligases are good molecular markers, allowing to study performance and health of fish following feeding trial and pathogen challenge. In addition, transcriptomic analysis performed to select further key molecular markers involved in a variety of processes and improved our knowledge of fish physiology and immunology, providing useful information for the development of new alternative diets for aquaculture.
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Grosh, Kimberly Coile. "Nutrigenomics and Nutritional Epigenetics – The State of the Science in Academia." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1308247018.

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7

Chankova, Nelly. "Establishing the influence of dietary fatty acids on the colon through nutrigenomics." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/establishing-the-influence-of-dietary-fatty-acids-on-the-colon-through-nutrigenomics(26dc700d-4e62-420c-959d-2dcab0cb363a).html.

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Introduction: The fatty acid (FA) composition of the diet can have both a positive and negative impact on the health and wellbeing of an individual. Diets rich in saturated FAs and cholesterol promote cardiovascular disease, while diets rich in omega 3 FA protect against cardiovascular disease. Diets rich in omega 6 FAs are thought to have pro-inflammatory and promoting properties, while diets rich in omega 3 FAs have anti-inflammatory and chemo preventative qualities. The increase of the ratio of omega 6 to omega 3 FAs is an important factor in the increased incidence of inflammatory diseases such as inflammatory bowel disease, cancer, and heart disease. The aim of this project was to find how the different FA composition of the diet would affect the phenotype of healthy mice. Methods: C57BL6 mice were fed diets enriched with fish oil, safflower oil, or lard, in order to produce diets rich in omega 3 PUFAs (Fish oil - FO), omega 6 PUFAs (Safflower oil - SO) or saturated FA enriched (Lard). Colonic epithelial cells (CECs) were used to determine the length of time necessary to see changes in the FA profile measured with gas chromatography. Gas chromatography was used to determine the changes in the FA profile of whole ascending colon due to changes in the FA composition of the diet. An Affymetrix array experiment was done to look for changes in the transcriptome of the ascending colon in effect of the different composition of the diets used. Changes in the tight junction protein expression in the whole ascending were measured with western blotting and fluorescent immunohistochemistry. Main Results: Changing the diet from standard maintenance chow to a high fat FO diet caused significant changes in the FAs composition of the CEC within 10 days. FO and SO diets produced mismatched changes in the omega 3 and omega 6 FAs, which caused a significant 4.8 fold increase of the omega 3/omega 6 FA ratio in the lipids extracted from mice fed the FO diet, and a small decrease in the lipids extracted from mice fed the SO diet. The diets employed produced only very small or negligible changes in the trasncriptome of the ascending colon. The diets did affect the expression of the tight junction proteins. Expression of claudin 2 and claudin 12 increased in the colons of all mice fed the experimental diets, although the increase was significant only in the samples from mice fed the lard enriched diet. Conclusions: Modifying the dietary FA composition can cause significant changes in the FA profile of the colonic epithelium within 10 days and the ascending colon within 15 days. However, these changes had a negligible effect on the transcriptome of the ascending colon. The changes in the FA composition of the colon did, however, cause changes in the TJ protein expression depending on the FA composition of the diet.
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Quinn, Peter. "Applications of functional nutrition and nutrigenomics to improve public health through dietary interventions." Thesis, University of Liverpool, 2018. http://livrepository.liverpool.ac.uk/3023632/.

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Diet and lifestyle factors are well documented for their impact on health and wellbeing. Epigenetics provides the added connection between personal genetics and environmental factors, including food, interacting with health and disease. Functional foods is a growth area of food development, augmentation and supplementation. However, more scientific validation of the claims made for functional foods and functional components is required to properly inform consumers and healthcare practitioners. There is also growing consumer acceptance of personalised genetic analysis for health and wellbeing. The commerciality of providing cost-effective genetic diet and lifestyle advice is a new and developing area in the health industry. All diseases have a genetic link, and genome-wide association studies (GWAS) are discovering genetic variations linked to complex diseases. However, nutrient information is absent for the development of dietary advice and the management and prevention of disease. The development of nutrigenomics provides information on the gene/nutrient interaction essential for the design of personalised nutrition. Functional nutrition from a combination of personalised genetic analysis and nutrigenomic interventions, represent an important new nexus for improving public health and the future of disease prevention.
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Tarasov, Stanislav. "Business solution for a food service company based on a modern nutrition concept (case of Russia)." Master's thesis, Vysoká škola ekonomická v Praze, 2011. http://www.nusl.cz/ntk/nusl-114364.

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Increasing level of public concerns about ageing and obesity problems accompanied by the advent of more and more health conscious consumers have put a priority on the health and wellness industry development which has started transformation from a niche category towards the mainstream. As a human being is an individual with unique known characteristics (like age, gender, health state, lifestyle) and less known characteristics like a genetic predisposition, the nutrition plan should be designed around these characteristics. Being aware of genetic predisposition of an individual allows to develop the appropriate health strategy for the particular individual. A systematization of these individual programs would support the development of a new generation of health practitioners. Russia is experiencing serious demographic problems with decreasing population and low life expectancy; high mortality rate from heart diseases and quite high obesity rates. It is expected that nutrigenomics concepts can be successfully developed in Russia due to its solid scientific base, relatively high level of medicine and the ever increasing awareness of the need for a healthy quality life especially within young generation. The goal of the thesis therefore is to analyze the key trends in the global and Russian food industries and develop a business idea of commercializing the personalized nutrition concept in the Russian food service market.
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BOMBA, LORENZO. "Effect of dietary changes during weaning on gut gene expression in animal models." Doctoral thesis, Università Cattolica del Sacro Cuore, 2012. http://hdl.handle.net/10280/1314.

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Una dieta scorretta incrementa il rischio di malattie come l’insulino resistenza e l’obesità. Questa tesi ha l’obiettivo di valutare l’effetto di diete sbilanciate sulla fisiologia ed espressione genica in topi e suini allo svezzamento. Topi C57BL/6 sono stati sacrificati dopo 2 settimane, dopo essere stati alimentati con dieta iper-lipidica e dieta controllo. L’espressione genica è stata stimata usando la tecnologia microarray. Quattro dei sette geni identificati differenzialmente espressi tra il controllo e l’iper-lipidico sono coinvolti nella regolazione della via metabolica del sistema circadiano, che recentemente è stato mostrato avere effetti sul metabolismo lipidico e processo infiammatorio. Il secondo studio ha avuto lo scopo di capire gli effetti dello svezzamento con o senza l’aggiunta di acidificante nella dieta. I suinetti allo svezzamento (T0) sono stati comparati con i suinetti dopo una settimana (T1). Il gruppo post-svezzamento è stato alimentato con una dieta convenzionale, e metà di questi hanno ricevuto un supplemento di acido sorbico. L’aggiunta di acido sorbico nella dieta non ha causato nessuna differenza a livello fisiologico e di espressione genica. 205 geni sono stati identificati come differenzialmente espressi in T1 comparato con T0, evidenziando una forte risposta all’adattamento metabolico e agli stress subiti durante lo svezzamento.
An incorrect diet increases the risk of diseases as insulin resistance and obesity. This thesis aims at assessing the effects of unbalanced diets on gut physiology and gene expression in pig and mouse during weaning. The first research explored the impact of a high fat diet in C57BL/6 mice. High-fat-fed mice and control-fed mice were sacrificed after two weeks of treatment. Gene expression level was assessed by 90K Combimatrix microarray technology. Four of seven genes found differentially expressed between control and high fat diet mice are involved in the regulatory pathway of the circadian clock system, which was recently shown to affect lipid metabolism and inflammatory processes. Those genes were successfully validated by real time PCR. The second study aimed at understanding the weaning effect with or without acidifier addition in the diet. Piglets at weaning (T0) were compared to piglets after one week (T1). The post-weaning group was fed a conventional diet, half of which received in addition sorbic acid. The sorbic acid supplementation evidenced no effects in terms of physiology and gene expression. 205 genes were significantly differentially expressed in T1 when compared with T0, evidencing a response to the metabolic adaptation and the stress suffered during weaning.
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Vaqué, Marquès Montserrat. "In silico studies of the effect of phenolic compounds from grape seed extracts on the activity of phosphoinositide 3-kinase (PI3K) and the farnesoid x receptor (FXR)." Doctoral thesis, Universitat Rovira i Virgili, 2007. http://hdl.handle.net/10803/8664.

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In silico studies of the effect of phenolic compounds from grape seed extracts on the activity of phosphoinositide 3-kinase (PI3K) and farnesoid X receptor (FXR)

Montserrat Vaqué Marquès
En aquesta tesis es pretén aplicar metodologies computacionals (generació de farmacòfors i docking proteïna lligand) en l'àmbit de la nutigenòmica (ciència que pretén entendre, a nivell molecular, com els nutrients afecten la salut). S'aplicaran metodologies in silico per entendre a nivell molecular com productes naturals com els compostos fenòlics presents en la nostra dieta, poden modular la funció d'una diana comportant un efect en la salut. Aquest efecte es creu que podria ser degut a la seva interacció directa amb proteïnes de vies de senyalització molecular o bé a la modificació indirecta de l'expressió gènica. Donat que el coneixement de l'estructura del complex lligand-receptor és bàsic per entendre el mecanisme d'acció d'aquests lligands s'aplica la metodologia docking per predir l'estructura tridimensional del complex. En aquest sentit, un dels programes de docking és AutoGrid/AutoDock (un dels més citats). No obstant, l'automatització d'AutoGrid/AutoDock no és trivial tan per (a) la cerca virtual en una llibreria de lligands contra un grup de possibles receptors, (b) l'ús de flexibilitat, i (c) realitzar un docking a cegues utilitzant tota la superfície del receptor. Per aquest motiu, es dissenya una interfície gràfica de fàcil ús per utilitzar AutoGrid/AutoDock. Blind Docking Tester (BDT) és una aplicació gràfica que s'executa sobre quatre programes escrits en Fortran i que controla les condicions de les execucions d'AutoGrid i AutoDock. BDT pot ser utilitzat per equips d'investigadors en el camp de la química i de ciències de la vida interessats en dur a terme aquest tipus d'experiments però que no tenen suficient habilitats en programació.

En la modulació del metabolisme de la glucosa, treballs in vivio i in vitro en el nostre grup de recerca s'han atribuït els efectes beneficiosos de l'extracte de pinyol de raïm en induir captació de glucosa (punt crític pel manteniment de l'homeostasis de la glucosa). No obstant alguns compostos fenòlics no tenen efecte en la captació de la glucosa, d'altres l'inhibeixen reversiblement. En alguns casos aquesta inhibició és el resultat de la competició dels compostos fenòlics amb ATP pel lloc d'unió de l'ATP de la subunitat catalítica de la fosfatidil inositol 3-kinasa (PI3K). Estudis recents amb inhibidors específics d'isoforma han identificat la p110α (la subunitat catalítica de PI3Kα) com la isoforma crucial per la captació de glucosa estimulada per insulina en algunes línies cel·lulars. Els programes computacionals han estat aplicats per tal de correlacionar l'activitat biològica dels compostos fenòlics amb informació estructural per obtenir una relació quantitativa estructura-activitat (3D-QSAR) i obtenir informació dels requeriments estructura-lligand per augmentar l'afinitat i/o selectivitat amb la diana (proteïna). Tot hi haver-se demostrat que l'adició d'extractes de compostos fenòlics en l'aliment pot tenir en general un benefici per la salut, s'ha de tenir en compte que l'estudi 3D-QSAR (construït a partir d'inhibidors sintètics de p110α) prediu que algunes d'aquestes molècules poden agreujar la resistència a la insulina en individus susceptibles dificultant la capatació de glucosa en múscul i teixit adipós i, per tant, produir un efecte secundari indesitjat.

Resultats en el nostre grup de recerca han demostrat que compostos fenòlics presents en extractes de llavor de raïm incrementen l'activitat del receptor "farnesoid x receptor" (FXR) de manera dosi depenent quan el lligand natural de FXR (CDCA) és present. Les metodologies in silico, docking i 3D-QSAR, han estat aplicades juntament amb dades biològiques d'agonistes no esteroidals de FXR que s'uneixen a un lloc d'unió proper però diferent al lligand esteroidal 6CDCA. Els resultats han mostrat que els compostos fenòlics no són capaços d'activar FXR per ells mateixos però poden afegir noves interaccions que estabilitzarien la conformació activa de FXR en presència del lligand natural CDCA. Els compostos fenòlics podrien induir canvis conformacionals específics que augmentarien l'activitat de FXR.



In silico studies of the effect of phenolic compounds from grape seed extracts on the activity of phosphoinositide 3-kinase (PI3K) and farnesoid X receptor (FXR)

Montserrat Vaqué Marquès
This thesis was written with the aim of applying computational methods that have already been developed for molecular design and simulation (i.e. pharmacophore generation and protein-ligand docking) to nutrigenomics. So, in silico tools that are routinely used by the pharmaceutical industry to develop drugs have been used to understand, at the molecular level, how natural products such as phenolic compounds (i.e. molecules that are commonly found in fruits and vegetables) can improve health and prevent diseases. Therefore, we first focused on predicting the structure of protein-ligand complexes. The docking algorithms can use the individual structures from receptor and ligand to predict (1) whether they can form a complex and (2) if so, the structure of the resulting complex. This prediction can be made, for instance, with AutoGrid/AutoDock, the most cited docking software in the literature. The automation of AutoGrid/AutoDock is not trivial for tasks such as (1) the virtual screening of a library of ligands against a set of possible receptors; (2) the use of receptor flexibility and (3) making a blind-docking experiment with the whole receptor surface. Therefore, in order to circumvent these limitations, we have designed BDT (i.e. blind-docking tester; http://www.quimica.urv.cat/~pujadas/BDT), an easy-to-use graphic interface for using AutoGrid/AutoDock. BDT is a Tcl/Tk graphic front-end application that runs on top of four Fortran programs and which controls the conditions of the AutoGrid and AutoDock runs.

As far as the modulation of the glucose metabolism is concerned, several in vivo and in vitro results obtained by our group have shown that grape seed procyanidin extracts (GSPE) stimulate glucose uptake in 3T3-L1 adipocytes and thus help to maintain their glucose homeostasis. In contrast, it is also well known that although some phenolic compounds do not affect glucose uptake, others reversibly inhibit it in several cell lines. Moreover, for at least some of these phenolic compounds, this inhibition is the result of their competition with ATP for the ATP-binding site in p110α (i.e. the α isoform of the catalytic subunit of phosphoinositide 3-kinase or PI3Kα). Furthermore, recent studies with isoform-specific inhibitors have identified p110α as the crucial isoform for insulin-stimulated glucose-uptake in some cell lines. Therefore, although it has been proved that the addition of phenolic compound extracts to food can have an overall benefit on health, it should be taken into account that some of these molecules may exacerbate insulin resistance in susceptible individuals via impaired glucose uptake in muscle and adipose tissues and, therefore, produce an undesirable side effect. In this context, we have applied computational approaches (i.e. protein-ligand docking and 3D-QSAR) to predict the IC50 (i.e. the concentration that reduces the p110α activity to 50%). Our results agree with previous experimental results and predict that some compounds are potential inhibitors of this enzyme.

Recent results in our research group have demonstrated that the phenolic compounds in GSPE increase the activity of the farnesoid X receptor (i.e. FXR) in a dose-dependent way when the natural ligand of FXR (i.e. CDCA) is also present. The phenolic compounds might induce specific conformational changes that increase FXR activity and then contribute to cardioprotection through mechanisms that are independent of their intrinsic antioxidant capacities but that involve direct interaction with FXR to modulate gene expression. Taking into account this hypothesis a 3D-QSAR analysis was made in an attempt to understand how phenolic compounds activate FXR. So, our results explain why phenolic compounds cannot activate FXR by themselves and how they can add new interactions to stabilize the active conformation of FXR when its natural ligand (i.e. CDCA) is present. Therefore, we proposed a mechanism of FXR activation by dietary phenolic compounds in which they may enhance bile acid-bound FXR activity.
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Landell, Carolina de Almeida Coelho. "Proteômica em dois grupos metabólicos de crianças e adolescentes com diferente perfil lipídico e glicídico submetidos à suplementação de micronutrientes." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/17/17144/tde-06042018-104807/.

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Introdução: Conhecer as respostas proteômicas de diferentes grupos metabólicos após uma intervenção nutricional poderia ajudar a identificar biomarcadores e o tratamento dietético mais apropriado para diferentes perfis de indivíduos. Objetivos: Descrever dois diferentes grupos metabólicos em um estudo de intervenção nutricional; descrever o perfil lipídico, os níveis de glicose e os dados proteômicos ao longo do estudo nesses dois grupos. Metodologia: Foi realizado um estudo de intervenção \"N-of-1\", com indivíduos de 9 a 13 anos, no qual ocorreu avaliação antropométrica, de composição corporal, de ingestão alimentar, bioquímica e proteômica em três momentos: no início do estudo (momento 1), após 6 semanas de suplementação diária de micronutrientes (momento 2), e após outras 6 semanas sem nenhuma intervenção (momento 3). A técnica estatística \"k-means clustering\" foi utilizada para alocar os participantes em dois grupos metabólicos distintos (cluster 1 e cluster 2), de acordo com os perfis glicídicos e lipídicos (glicemia, triglicerídeos, colesterol total, LDL, HDL e VLDL colesterol) que os indivíduos apresentaram nos três momentos do estudo. Resultados: O cluster 1 (n = 111) teve melhor perfil glico-lipídico e também apresentou menores valores para índice de massa corporal, circunferência de cintura e porcentagem de gordura corporal nos três momentos do estudo, comparado ao cluster 2 (n = 25). A ingestão alimentar não diferiu entre os clusters em nenhum momento do estudo. Com a suplementação de micronutrientes, o cluster 1 apresentou redução de glicemia, LDL e colesterol total, além de diminuir sua ingestão de energia, carboidrato, lipídeo e proteína, enquanto o cluster 2 reduziu LDL, colesterol total e HDL e não alterou sua ingestão de energia e macronutrientes. Foi identificada a expressão de 20 proteínas no plasma dos indivíduos dos clusters 1 e 2, sendo que a maioria delas evoluiu de maneira diferente entre os dois grupos após a intervenção. Com a suplementação, o cluster 1 apresentou aumento na expressão de alpha-1-acid glycoprotein 1, alpha- 2-HS-glycoprotein, ceruloplasmin e de fibrinogen alpha, beta e gamma chain, bem como redução na expressão de apolipoprotein A-IV, haptoglobin, Ig alpha-1 chain C region, serotransferrin e vitamin D-binding protein. No mesmo período, o cluster 2 mostrou aumento de alpha-1-antitrypsin, ceruloplasmin, haptoglobin, Ig alpha-1 chain C region e plasma protease C1 inhibitor, além de diminuição na expressão de alpha-1-acid glycoprotein 1 e de fibrinogen alpha, beta e gamma chain. Conclusões: É possível que tenha ocorrido aumento de expressão de proteínas que podem ter auxiliado na melhora do perfil glico-lipídico dos participantes. O cluster de pior perfil parece ter se beneficiado mais com a intervenção em relação à expressão de proteínas do que o cluster de melhor perfil. O estudo do perfil genético poderia ajudar no entendimento da resposta metabólica dos indivíduos.
Introduction: Knowing the proteomic responses from different metabolic groups after a nutritional intervention could help to identify biomarkers and the most appropriate dietary treatment for different profiles of subjects. Aims: To describe two different metabolic groups in a nutritional intervention study; To describe the lipid profile, glucose levels and proteomic data throughout the study in these two groups. Methodology: An \"N-of-1\" intervention study was carried out with subjects from 9 to 13 years of age, in which anthropometric, body composition, food intake, biochemical and proteomics evaluation was performed in three moments: at the beginning of the study (moment 1), after 6 weeks of daily micronutrient supplementation (moment 2), and after another 6 weeks without any intervention (moment 3). The \"k-means clustering\" technique was used to allocate the participants to two distinct metabolic groups (cluster 1 and cluster 2) according to the glucose and lipid profiles (glycemia, triglycerides, total cholesterol, LDL, HDL and VLDL cholesterol) that these subjects presented at the three moments of the study. Results: Cluster 1 (n = 111) had a better glycemic and lipid profile and also presented lower values for body mass index, waist circumference and body fat percentage in the three moments of the study, compared to cluster 2 (n = 25). Food intake did not differ between the clusters in any moment of the study. With supplementation, cluster 1 showed a decrease in glycemia, LDL and total cholesterol, as well as decreased energy, carbohydrate, lipid and protein intake, while cluster 2 reduced LDL, total cholesterol and HDL and did not alter its energy and macronutrients intake. It was identified the expression of 20 proteins in the plasma of the subjects from clusters 1 and 2, and most of them evolved differently between the two groups after the intervention. Cluster 1 showed increase in expression of alpha-1-acid glycoprotein 1, alpha-2-HS-glycoprotein, ceruloplasmin and alpha, beta and gamma chain fibrinogen, as well as reduction in expression of apolipoprotein A-IV, haptoglobin, Ig alpha-1 chain C region, serotransferrin and vitamin D-binding protein. In the same period, cluster 2 showed an increase of alpha-1-antitrypsin, ceruloplasmin, haptoglobin, Ig alpha-1 chain C region and plasma protease C1 inhibitor, as well as decrease in the expression of alpha-1- acid glycoprotein 1 and alpha fibrinogen, beta and gamma chain. Conclusions: It is possible that there was occurred an increase in the expression of proteins that may have helped to improve glycemic and lipid profiles of the participants. The worst-profile cluster seems to have benefited more from the intervention in relation to protein expression than the cluster with the best profile. The study of the genetic profile could help in the understanding of the individuals metabolic response.
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Coelho, Carolina de Almeida. "Perfil metabólico e do estado nutricional de crianças e adolescentes de escolas da cidade de Ribeirão Preto, São Paulo, Brasil." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/17/17144/tde-11032014-090751/.

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Introdução: Poucos trabalhos correlacionam o perfil metabólico com o estado nutricional em crianças e adolescentes após intervenção dietética. Objetivos: Identificar, em uma população de indivíduos de 9 a 13 anos submetidos a uma intervenção nutricional, a existência de diferentes grupos metabólicos formados com base em dados bioquímicos (níveis de glicemia, colesterol total, triglicérides, VLDL colesterol, LDL colesterol e HDL colesterol) coletados em 3 momentos do estudo; e descrever a evolução longitudinal do perfil nutricional e metabólico destes grupos. Metodologia: Estudo clínico de intervenção auto-controlado, baseado na medida do perfil bioquímico (níveis de glicemia, colesterol total, triglicérides, VLDL colesterol, LDL colesterol e HDL colesterol) e do estado nutricional (antropometria, composição corporal e dados de ingestão alimentar) em três momentos: no início do estudo (antes de ser iniciada a intervenção), após seis semanas de suplementação de vitaminas e minerais e após outras seis semanas sem essa intervenção, para avaliar como um indivíduo, de 9 a 13 anos de idade responde à suplementação de múltiplos micronutrientes. O nível de atividade física praticado por esses indivíduos foi avaliado através do aparelho Bodybugg®. Resultados: Cento e trinta e seis indivíduos foram estudados até o terceiro momento do estudo. 43,4% eram do sexo masculino e 56,6% eram do sexo feminino. A média de idade foi de 11,39 ± 1,10 anos. A maioria dos participantes pertenciam ao estadiamento puberal 2 (43,4%) e 3 (35,3%). Em relação à classificação econômica dos participantes, a maioria pertencia à categoria B2 (38,2%) e C1 (26,5%). Do total da amostra estudada, no momento 1, 4,4% dos participantes apresentaram magreza grave; 5,9% apresentaram magreza, 41,9% estavam com o peso adequado, 22,8% tinham sobrepeso e 25% tinham obesidade. No momento 2, 3,7% dos participantes apresentaram magreza grave, 7,4% apresentavam magreza, 42,6% tinham o peso adequado, 22,1% tinham sobrepeso e 24,3% tinham obesidade e no momento 3, 3,7% dos participantes apresentaram magreza grave, 6,6% apresentavam magreza, 41,2% tinham o peso adequado, 22,8% tinham sobrepeso e 25,7% tinham obesidade. Em média encontramos: 3,7% dos participantes com magreza grave, 5,9% com magreza, 41,9% com peso adequado, 24,3% com sobrepeso e 24,3% com obesidade. Os participantes foram agrupados (clusterizados) utilizando-se como critério seu perfil metabólico (níveis de glicemia, colesterol total, triglicérides, VLDL colesterol, LDL colesterol e HDL colesterol) nos três momentos do estudo, por meio da técnica estatística K-cluster. O cluster 1 (n = 111) era composto por mais indivíduos do sexo feminino que o cluster 2 (n = 25) (p = 0,006) e apresentou melhor perfil metabólico (melhores valores para o perfil lipídico e de glicemia). Os indivíduos do cluster 1 também apresentaram menor peso, índice de massa corporal (IMC), circunferência da cintura (CC) e massa gorda (% peso) quando comparado aos participantes do cluster 2. A massa corporal magra (% peso) e a água corporal total (% peso) foram estatisticamente maiores nos participantes do cluster 1. A análise da ingestão habitual (por questionário de frequência alimentar - QFA) mostrou que os participantes do cluster 1 estavam ingerindo mais vitamina B2 e vitamina B6 quando comparados aos participantes do cluster 2 (p < 0.05). Houve menores valores para proteína C-reativa (PCR) e maiores valores para ferro sérico no cluster 1. A capacidade latente de ligação de ferro (UIBC) e leucócitos foram estatisticamente maiores no cluster 2. Não houve diferença entre o nível de atividade física praticado pelos dois clusters, ambos desempenhavam atividade física leve. A análise longitudinal mostrou que houve aumento de estatura e peso nos clusters 1 e 2. A avaliação longitudinal da ingestão habitual (QFA) no cluster 1 mostra redução da ingestão de energia, carboidrato, proteína e lipídio do momento 1 (M1) para momento 2 (M2) e momento 3 (M3). A suplementação de vitaminas mostrou resultados estatísticos significativos, consistentes com suplementação e wash out para a maioria das vitaminas e minerais nos clusters 1 e 2. A análise longitudinal (corrigindo para as variáveis idade, gênero, estadiamento puberal e ingestão de energia, carboidrato e lipídio) no cluster 1 mostrou que o colesterol total e a LDL diminuíram ao longo do estudo; a glicemia diminuiu do momento 1 para o momento 2, porém PCR aumentou no momento 2; ferro sérico e hemoglobina diminuíram no momento 2 e aumentaram no momento 3. No cluster 2, o colesterol total e o LDL diminuíram ao longo do estudo; a PCR aumentou ao longo do estudo, ferro sérico diminuiu do momento 1 para o momento 2. Conclusões: Foram encontrados dois grupos metabólicos opostos. Os indivíduos podem responder de forma diferente a uma mesma intervenção e é possível que a suplementação de múltiplos micronutrientes tenha um papel na melhora do perfil glicídico e lipídico de alguns sujeitos do estudo. Estudos de genotipagem e proteômica poderão reforçar esta hipótese e ajudar a entender como o sistema biológico de crianças e adolescentes interage para culminar em uma resposta frente a uma intervenção.
Introduction: Few studies have correlated metabolic profile and nutritional status in children and adolescents after dietary intervention . Objectives: To identify the existence of different metabolic groups formed by individuals 9-13 years undergoing nutritional intervention through biochemical data (glucose levels, total cholesterol, triglycerides, VLDL cholesterol, LDL cholesterol and HDL cholesterol) collected in three stages of the study, and to describe the longitudinal evolution of the nutritional and metabolic profile in these groups. Methodology: Clinical intervention self-controlled study, based on measuring the biochemical profile (glucose levels, total cholesterol, triglycerides, VLDL cholesterol, LDL cholesterol and HDL cholesterol) and nutritional status (anthropometry, body composition and dietary intake data) at three times: at baseline (before the intervention started), after six weeks of supplementation of vitamins and minerals and after more six weeks without this intervention, to assess how an individual, 9-13 years old answered the multiple micronutrient supplementation. Physical activity level was also assessed through a tool called bodybugg®. Results: One hundred and thirty six subjects were studied until the third moment of the data collection. 43.4% were male and 56.6% were female. The average age was 11.39 ± 1.10 years. Most participants belonged to pubertal stage 2 (43.4%) and 3 (35.3%). Regarding the economic status of the participants, the majority belonged to the category B2 (38.2%) and C1 (26.5%). Of the total sample, at moment 1, 4.4% of participants had severe underweight, 5.9% were underweight, 41.9% were with the proper weight, 22.8% were overweight and 25% were obese. At the moment 2, 3.7% of participants had severe underweight, 7.4% were underweight, 42.6% had normal weight, 22.1% were overweight and 24.3% were obese. And at the moment 3, 3.7% of participants had severe thinness, 6.6% were underweight, 41.2% had normal weight, 22.8% were overweight and 25.7% were obese. On average we found: 3.7% of participants with severe thinness, 5.9% with malnutrition, 41.9% with adequate weight, 24.3% overweight and 24.3% obese. The clustering of the participants used as criteria the metabolic profile (glucose levels, total cholesterol, triglycerides, VLDL cholesterol, LDL cholesterol and HDL cholesterol) of the three stages of the study through the statistical approach K - cluster. Cluster 1 (n = 111) had a higher proportion of females when compared to cluster 2 (n = 25) (p = 0.006) and better metabolic profile (lipid and glycemia). Participants who had better metabolic profile (cluster 1) showed lower weight, body mass index (BMI), waist circumference (WC) and fat mass (weight %) when compared to participants in cluster 2. Lean body mass (weight %) and total body water (% weight) were statistically higher in participants in cluster 1. The analysis of the habitual intake (food frequency questionnaire - FFQ) showed that participants in cluster 1 were had higher intake of vitamin B2 and vitamin B6 when compared to cluster 2 (p < 0,05). Cluster 1 also showed higher values C - reactive protein (CRP) and higher levels of iron. The latent capacity for iron binding (UIBC) and leukocytes were higher in cluster 2. There was no difference between the level of physical activity practiced by clusters 1 and 2, both had light physical activity. Longitudinal analysis showed that there was an increase in height and weight in clusters 1 and 2. A longitudinal assessment of usual intake (FFQ) in cluster 1 showed reduced intake of energy, carbohydrate, protein and lipid from moment 1 (M1) to moment 2 (M2) and moment 3 (M3). Supplementation with vitamins showed significant statistical results, consistent with supplementation and washout for most vitamins and minerals in clusters 1 and 2. A longitudinal analysis (correcting for age, gender, pubertal stage, and energy intake, carbohydrate and lipid) in cluster 1 showed that total cholesterol and LDL decreased throughout the study, blood glucose decreased from time 1 to time 2, but CRP increased in moment 2; hemoglobin and serum iron decreased from 1 to 2 and from 1 to 3. In cluster 2, total cholesterol and LDL decreased throughout the study, CRP increased throughout the study, serum iron decreased from time 1 to time 2. Conclusions: We found two reverse metabolic groups. Individuals may respond differently to the same intervention, and it is possible that multiple micronutrient supplementation has a role in improving glycemia and lipid profile of some subjects. Genotyping and proteomics studies may reinforce this hypothesis and help understand how the biological system of children and adolescents interact to culminate in a response against an intervention.
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Lima, Ana Rita da Cunha. "Nutrigenómica." Master's thesis, [s.n.], 2014. http://hdl.handle.net/10284/4430.

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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
Numa sociedade cada vez mais preocupada com a saúde, a nutrição tem desempenhado um papel muito importante, não só com a causa da doença, mas também como uma forma de prevenção da doença. Isto ocorre porque os nutrientes são capazes de interagir com os mecanismos moleculares do organismo e assim, modificar as funções fisiológicas. A nutrigenómica (o estudo dos nutrientes na expressão dos genes) pode assim ser explorada de duas formas: os alimentos podem influenciar a atividade dos genes, e os genes podem influenciar a necessidade de certos nutrientes. Isto proporciona uma compreensão genética de como os componentes da dieta comum poderão afetar o equilíbrio entre a saúde e a doença, alterando desta forma a expressão e ou estrutura da composição genética de um individuo. Apesar de os indivíduos serem diferentes uns dos outros, o genoma é 99,9% semelhante entre eles. Esta diferença de 0.1% representa variações visíveis como a cor do cabelo, pele e olhos e diferenças mais subtis, como o aumento de predisposição para desenvolver doenças crónicas e a necessidade de determinados nutrientes e compostos bioativos. As várias mudanças nos hábitos alimentares e estilo de vida que surgem no dia-a-dia das pessoas podem assim estar relacionadas com o aparecimento de doenças influenciadas pela alimentação. Assim, lições de Nutrigenómica mostram a importância de consciencializar as pessoas para a importância da nutrição no estado de saúde de cada ser humano individual. No presente trabalho, pretende-se transmitir ao leitor uma visão compreensível mas ampla e detalhada de como a nutrigenómica é importante e quais as vantagens de usar esta ferramenta de estudo. In an increasingly health-conscious society, nutrition has played a very important role not only as the cause of disease but also as a way of disease prevention. This occurs because nutrients are able to interact with the organism’s molecular mechanisms and thereby modify physiological functions Nutrigenomics (the study of the influence of nutrients in gene expression) can thus be explored in two ways: food can influence the activity of genes and; genes can influence the need for certain nutrients. This provides an understanding of how the genetic components of common diets may affect the balance between health and disease, thereby altering the expression or structure and the genetic makeup of an individual. Despite being different from each other individual, the Human Genome is 99,9 % similar between individuals. This 0.1 % difference accounts for visible variations such in hair, skin and eye color and more subtle differences such as the increased predisposition to develop chronic diseases and the need for certain nutrients and bioactive compounds. The various changes in eating habits and lifestyle that arise in the day-to-day life of people can thus be related to the onset of diet-related disorders. Thus, lessons from Nutrigenomics indicate the importance of making people aware of the relevance of nutrition in the health status of every individual human being. The present work, aims at providing the reader with a comprehensive but broad and detailed view of how nutrigenomics is important and what are the advantages of using this study tool.
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Wilkins, Julianne G. "Knowledge and Perception of College Students Toward Genetic Testing for Personalized Nutrition Care." Kent State University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=kent1491906065477344.

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Almeida, Mara Ribeiro de. "Avaliação da citotoxicidade, genotoxicidade, antigenotoxicidade e expressão dos genes Tp53 e Ephx2 em ratos tratados com Caryocar villosum." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/60/60134/tde-21062013-101342/.

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O consumo de frutas e verduras está relacionado com a promoção da saúde porque tem sido associado com a redução do risco de desenvolvimento de doenças crônicas como, por exemplo, câncer e doenças degenerativas e cardiovasculares. Dessa forma, o estudo dos efeitos biológicos desses alimentos tem ganhado atenção nos últimos anos. O piquiá (Caryocar villosum) é um fruto nativo da Amazônia e é rico em compostos antioxidantes como os compostos fenólicos. Assim, o objetivo deste estudo foi avaliar os efeitos genotóxicos e antigenotóxicos in vivo da polpa liofilizada do piquiá e também de seu extrato etanólico. Além disso, os compostos fitoquímicos presentes na polpa e no seu extrato foram quimicamente determinados. Ratos Wistar foram tratados por gavagem, durante 14 dias consecutivos, com três diferentes doses da polpa do piquiá (75, 150 ou 300 mg/kg p.c.) ou com seu extrato etanólico (75 mg/kg p.c.). No 14° dia, os animais receberam solução salina (NaCl 0,9%, i.p.) ou doxorrubicina (DXR, 15 mg/kg p.c., i.p.) e após 24 horas foram eutanasiados. A medula óssea e o sangue periférico foram usados no teste do micronúcleo (MN), e o fígado, rins e coração foram utilizados nos ensaios do cometa, nas análises bioquímicas das substâncias reativas ao ácido tiobarbitúrico (TBARS) e glutationa reduzida (GSH) e na avaliação da expressão de mRNA dos genes epóxido hidrolase (Ephx2) e proteína tumoral p53 (Tp53). A polpa do piquiá não apresentou efeito genotóxico nem mutagênico em nenhuma das doses avaliadas, demonstrou atividade antigenotóxica e ainda reduziu os níveis de TBARS induzidos pela DXR no coração. Efeitos opostos foram encontrados para o extrato etanólico da polpa do piquiá, por apresentar genotoxicidade, mas não mutagenicidade, e indução de TBARS no coração. Os níveis de mRNA do gene Ephx2 no rim e coração foram aumentados após o tratamento com a maior dose da polpa do piquiá, entretanto, no rim a menor dose diminuiu a transcrição desse gene induzida pela DXR. No fígado as doses de 75 e 300 mg/kg p.c. diminuíram os níveis de mRNA do gene Ephx2 induzidos pela DXR. A dose de 300 mg/kg p.c. da polpa diminuiu a expressão de mRNA do gene Tp53 nos grupos da associação piquiá + DXR no fígado, rim e coração. O extrato etanólico da polpa do piquiá modulou a expressão de mRNA do gene Ephx2 apenas no fígado, aumentando os níveis desse transcrito, enquanto que no coração houve diminuição da transcrição do gene Tp53. Foi encontrada uma diferença de composição fitoquímica entre a polpa liofilizada e seu extrato etanólico. O extrato apresentou 1,4x mais compostos fenólicos e 3x menos carotenoides quando comparado com a polpa. Além disso, o ácido gálico foi o composto fenólico predominante na polpa, enquanto que no extrato o fenol mais abundante foi o ácido elágico. A diferença dos efeitos biológicos entre a polpa liofilizada do piquiá e seu extrato etanólico pode ser devido à alteração da composição fitoquímica.
Fruit and vegetables intake has been related to the promotion of health because it has been associated to reduced risk of chronic diseases development such as cancer, and cardiovascular and degenerative diseases. Thus, the study of the biological effects of these foods has increased in recent years. Piquiá (Caryocar villosum) is a fruit native of the Amazon and it is rich in antioxidant compounds such as phenolic compounds. Therefore, the aim of this study was to evaluate the in vivo genotoxicity and antigenotoxicity effects of the piquiá lyophilized pulp fruit and its ethanolic extract. Moreover, the phytochemical characterization of pulp and extract was determined. Wistar rats were treated by gavage, for 14 days, with three doses of piquiá pulp (75, 150 or 300 mg/kg b.w.) or with its ethanolic extract (75 mg/kg b.w.). On 14th day, the animals received saline (0.9% i.p.) or doxorubicin (DXR, 15 mg/kg b.w.) and after 24 hours they were euthanized. Bone marrow and peripheral blood were used in micronucleus (MN) test, and the liver, kidney and heart were used in comet assay, thiobarbituric acid reactive substances (TBARS), reduced gluthatione (GSH), and in the evaluation of mRNA expression of epoxide hydrolase (Ephx2) and tumor protein p53 (Tp53) genes. The piquiá pulp was not genotoxic nor mutagenic, demonstrated antigenotoxic effects and reduced the TBARS levels induced by DXR in heart. The ethanolic extract had opposite effects, whereas it was genotoxic, but not mutagenic, and increased the TBARS levels in heart. Ephx2 mRNA levels in kidney and heart were increased after treatment with the higher dose of piquiá pulp, however, in kidney the lowest dose decreased the transcription of this gene induced by DXR. In liver, the 75 and 300 mg/kg b.w. doses of piquiá pulp decreased the Ephx2 mRNA levels induced by DXR. The piquiá pulp 300 mg/kg + DXR group, presented lower levels of Tp53 mRNA in liver, kidney and heart. The ethanolic extract of piquiá pulp modulated the mRNA Ephx2 expression only in the liver, increasing the levels of this transcript, while in the heart decreased the transcription of Tp53 gene. There was a difference on phytochemical composition between the pulp and its ethanolic extract. The extract presented 1.4-fold more phenolic compounds and 3-fold less carotenoids than piquiá pulp. Furthermore, gallic acid was the predominant phenol in the pulp, whereas in the ethanolic extract the most abundant phenol was the ellagic acid. The difference in the biological effects between piquiá pulp and is ethanolic extract may be due the change of the phytochemical composition.
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17

Machado, Carla da Silva. "Avaliação da instabilidade genômica, estresse oxidativo e modulação da expressão gênica pela vitamina D em modelo de ratos espontaneamente hipertensos." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17135/tde-04012017-094931/.

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A vitamina D3 é um micronutriente obtido da dieta ou pela conversão do 7- dehidrocolesterol na epiderme após exposição à radiação UVB. A vitamina D (D2 ou D3) atua sobre o sistema renina-angiotensina-aldosterona, e sua deficiência vem sendo associada ao desenvolvimento da hipertensão. O objetivo deste estudo foi avaliar o efeito da suplementação ou deficiência de vitamina D3 em ratos espontaneamente hipertensos (SHR - spontaneously hypertensive rats) e seus controles normotensos (Wistar Kyoto - WKY) sobre a pressão arterial sistólica, danos ao DNA e cromossomos, marcadores bioquímicos do estresse oxidativo, burst oxidativo dos neutrófilos, análise de fibrose no rim e perfil de expressão de genes relacionados com a hipertensão arterial no rim e coração. Os animais foram alimentados com dieta controle (1.000 UI/kg), suplementada (10.000 UI/kg) ou deficiente (0 UI/kg) em vitamina D3 ao longo de 12 semanas. A quantificação plasmática de vitamina D3 foi avaliada pelo método ELISA (Enzyme-Linked Immunosorbent Assay) e a pressão arterial sistólica foi aferida semanalmente, por método não invasivo de pletismografia da artéria caudal. Os danos ao material genético foram avaliados pelo ensaio do cometa nas células do sangue periférico, rim e coração e pelo teste do micronúcleo nos eritrócitos da medula óssea e sangue periférico; o estresse oxidativo foi avaliado pelos ensaios de quantificação das substâncias reativas ao ácido tiobarbitúrico (TBARS - Thiobarbituric Acid Reactive Substances) e glutationa (GSH) no rim e coração; o burst oxidativo em neutrófilos do sangue periférico; a quantificação de fibrose por histologia renal e a expressão gênica por RT2 ProfilerTM PCR Arrays no rim e coração. Os resultados obtidos com os ratos SHR mostraram que a suplementação com vitamina D3 reduziu a pressão arterial sistólica, não induziu danos ao DNA e aos cromossomos, estresse oxidativo ou fibrose renal, e regulou a expressão de quatro genes envolvidos com a hipertensão arterial no rim (Ace, Agt, Ren e Edn1) e cinco genes no coração (Ace, Avp, Ephx2, Mylk3 e Ren). A deficiência em vitamina D3 aumentou a pressão arterial sistólica, os danos ao DNA e aos cromossomos, a peroxidação lipídica no rim e coração, o burst oxidativo dos neutrófilos, o percentual de fibrose no rim, e a expressão de treze genes envolvidos com a hipertensão arterial no rim (Ace, Acta2, Agt, Agtr1a, Agtr1b, Alox5, Cacna1c, Ece1, Ednra, Kcnma1, P2rx4, Scnn1g e Slc7a1) e nove genes no coração (Ace, Agtr1b, Cacna1c, Drd5, Mylk2, Nostrin, Scnn1a, Scnn1g e Sphk1). Nos animais WKY, a dieta suplementada alterou a expressão do gene Ren no rim e de dez genes no coração (Ace2, Bdkrb2, Drd3, Drd5, Itpr1, Itpr2, Itpr3, Ptgs1, Scnn1a e Scnn1g); e a dieta deficiente em vitamina D3 aumentou os danos ao DNA nos eritrócitos, induziu fibrose no rim e alterou a expressão de três genes no rim (Ace, Cps1 e Arg2) e de seis genes no coração (Ace, Cacna1c, Edrna, Ephx2, Itpr1 e Itpr2). Nos parâmetros pressão arterial sistólica, danos aos cromossomos, peroxidação lipídica e burst oxidativo, os ratos WKY alimentados com as dietas suplementada ou deficiente em vitamina D3 não diferiram em relação aos animais que receberam a dieta controle. Em conclusão, a variação da concentração de vitamina D3 da dieta alterou a fisiologia da hipertensão arterial, atuando como um anti-hipertensivo na suplementação e agravando os efeitos da hipertensão na deficiência.
Vitamin D3 is a micronutrient obtained from diet or by conversion of 7- dehydrocholesterol in the skin after exposure to UVB radiation. Vitamin D (D2 or D3) acts on the renin-angiotensin-aldosterone system, and its deficiency has been associated with hypertension development. This study aimed to evaluate the effect of vitamin D3 supplementation or deficiency in spontaneously hypertensive rats (SHR - spontaneously hypertensive rats) and their normotensive controls (Wistar Kyoto - WKY) on systolic blood pressure, DNA and chromosomes damage, biochemical markers of oxidative stress, oxidative burst in neutrophils, renal fibrosis and the gene expression profile of genes related to hypertension in kidney and heart. The rats were fed a vitamin D3 control diet (1,000 IU/kg) supplemented diet (10,000 IU/kg) or deficient diet (0 IU / kg) during 12 weeks. Vitamin D3 plasma quantification was performed by ELISA (Enzyme-Linked Immunosorbent Assay) technique and systolic blood pressure was measured weekly by noninvasive plethysmography of the caudal artery. DNA and chromosomal damage was evaluated by the comet assay in the peripheral blood, kidney and heart cells and by the micronucleus test in erythrocytes from bone marrow and peripheral blood; oxidative stress was evaluated by thiobarbituric acid reactive substances (TBARS) and glutathione (GHS) assays in kidney and heart; oxidative burst in neutrophils of peripheral blood; renal fibrosis by histology and gene expression by RT2 ProfilerTM PCR Arrays in kidney and heart. The results obtained for SHR rats showed that vitamin D3 supplementation reduced systolic blood pressure, did not induced DNA or chromosomal damage, oxidative stress or renal fibrosis, and regulated the expression of four genes involved with hypertension in the kidney (Ace, Agt, Ren and Edn1) and five genes in the heart (Ace, Avp, Ephx2, Mylk3 and Ren). Vitamin D3 deficiency increased systolic blood pressure, DNA damage in erythrocytes, lipid peroxidation in kidney and heart, oxidative burst in neutrophils and the renal fibrosis, and regulates the expression of thirteen genes involved with hypertension in kidney (Ace, Acta2, Agt, Agtr1a, Agtr1b, Alox5, Cacna1c, Ece1, Ednra, Kcnma1, P2rx4, Scnn1g and Slc7a1) and nine genes in heart (Ace, Agtr1b, Cacna1c, Drd5, Mylk2, Nostrin, Scnn1a, Scnn1g and Sphk1). In WKY rats, vitamin D3 supplementation altered the expression of Ren gene in the kidney and of ten genes in the heart (Ace2, Bdkrb2, Drd3, Drd5, Itpr1, Itpr2, Itpr3, Ptgs1, Scnn1a and Scnn1g); and vitamin D3 deficiency increased DNA damage in erythrocytes and renal fibrosis, and altered the expression of three genes in the kidney (Ace, Cps1 and Arg2) and six genes in the heart (Ace, Cacna, Ednra, Ephx2, Itpr1 and Itpr2). In the parameters systolic blood pressure, chromosomal damage, lipid peroxidation and oxidative burst, WKY rats fed with vitamin D3 supplemented or deficient diet did not differ compared to rats that received vitamin D3 control diet. In conclusion, the variation of dietary vitamin D3 levels altered the physiology of hypertension, acting as an antihypertensive in supplementation and aggravating the hypertension effects in its deficiency.
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18

Serpeloni, Juliana Mara. "Atividade antigenotóxica de compostos da dieta e sua influência na expressão de genes de resposta ao estresse oxidativo." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/60/60134/tde-04072012-111234/.

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Os pigmentos naturais, além de fornecerem cor e beleza aos diferentes organismos, desempenham importantes funções e ações biológicas, como as funções vitais de fotossíntese, respiração celular e a ação antioxidante. Assim, o presente estudo investigou os potenciais citotóxicos, genotóxicos e protetores dos pigmentos naturais clorofila b (CLb) e luteína (LT), isolados e em combinação, em doses normalmente consumidas na dieta. Para isso foram utilizados o teste do micronúcleo em células da medula óssea e do sangue periférico e o ensaio cometa em células do sangue periférico, rim e fígado de camundongos. Também foram avaliados parâmetros bioquímicos de estresse oxidativo, glutationa e substâncias reativas ao ácido tiobarbitúrico no rim e no fígado, além de glutationa e catalase no sangue periférico, a fim de investigar o papel antioxidante desses pigmentos. A capacidade da LT de alterar a expressão de genes de resposta ao estresse oxidativo e defesa antioxidante foi avaliada no tecido hepático dos camundongos utilizando a técnica de PCR em tempo real (RT-qPCR) array. Para a verificação da atividade protetora dos pigmentos, a cisplatina (cDDP) foi utilizada como indutor de danos oxidativos e ao DNA. Adicionalmente, foram avaliados os potenciais citotóxicos, genotóxicos e antioxidantes da LT em cultura de células de hepatocarcinoma humano por meio do teste do MTT [3-(4,5-dimetil-2-tiazolil)-2,5-difenil-2H-tetrazólio], ensaio cometa e avaliação de parâmetros bioquímicos de estresse oxidativo, a fim de se estabelecer comparações entre resultados in vitro e in vivo, bem como propor mecanismos de ação para os efeitos antigenotóxicos da LT. Nossos resultados mostraram que os tratamentos com os pigmentos, tanto a LT quanto a CLb, isolados ou em combinação não causaram qualquer dano ao material genético nos testes empregados e ofereceram proteção frente aos danos induzidos no DNA pela cDDP tanto in vitro como in vivo. Efeitos antioxidantes para ambos pigmentos foram observados no sangue periférico e nos tecidos renais e hepáticos, e a LT também melhorou os parâmetros de estresse oxidativo avaliados in vitro. Na avaliação da expressão de genes de resposta ao estresse oxidativo em células do fígado de camundongos, a cDDP diminuiu a expressão 16 genes, entre eles, importantes genes responsáveis pela manutenção do estado redox da célula. Além disso, a LT mostrou que pode atuar como antioxidante não só agindo diretamente no seqüestro de radicais livres, mas também, induzindo a expressão de 11 dos 84 genes avaliados, e de 15 genes quando associada à cDDP. Em resumo, nossos resultados mostraram que a LT e a CLb, isoladas ou em combinação, nas doses consumidas normalmente na dieta, podem contribuir para a promoção da saúde considerando seus efeitos antigenotóxicos e antioxidantes.
The natural pigments, in addition to providing color and beauty to the different organisms, play important biological role, including the vital functions of photosynthesis, cellular respiration and antioxidant action. Thus, this study investigated the genotoxic and protective potential of natural pigments, alone and in combination, chlorophyll b (CLb) and lutein (LT), in concentrations usually consumed in the diet. For this purpose, we used the micronucleus test in bone marrow and peripheral blood cells and the comet assay in peripheral blood, kidney and liver of mice. Biochemical parameters of oxidative stress were also evaluated, such as glutathione and thiobarbituric acid reactive substances in the kidney and liver and catalase and glutathione in peripheral blood in order to investigate the antioxidant properties of these pigments. The ability of lutein to alter the expression of genes involved in oxidative stress response and antioxidant defense was evaluated in liver tissue of mice using the technique of real-time PCR (RT-qPCR) array. To verify the protective activity of the pigments, cisplatin (cDDP) was used as an inducer of oxidative stress and DNA damage. Additionally, we assessed the genotoxic and antioxidant potential of LT in cell cultures of human hepatocellular carcinoma using the test of MTT [3 - (4,5-dimethyl-2-thiazolyl) -2,5-diphenyl-2H-tetrazolium], comet assay and assessment of biochemical parameters of oxidative stress, in order to make comparisons between results in vitro and in vivo, as well to propose mechanisms to antigenotoxic effects of LT. Our results showed that treatment with the pigments, both the LT and the CLb, alone or in combination, did not cause any DNA damage in the tests employed and offered protection against DNA damage induced by cDDP in both in vitro and in vivo. Antioxidant effects were observed for both pigments in peripheral blood, kidney and liver, and LT also improved the oxidative stress parameters measured in vitro. In the evaluation of the expression of genes involved in response to oxidative stress in liver cells of mice, cDDP decreased the expression of 16 genes, among them, important genes responsible for maintaining the redox status of the cell. Moreover, LT showed that it can act as an antioxidant not only acting directly in the scavenging of free radicals, but also by inducing the expression of 11 of the 84 genes evaluated and 15 when LT was associated to cDDP. In summary, our results showed that the LT and CLb, alone or in combination, at concentrations usually consumed in the diet can contribute to health promotion considering their antigenotoxic and antioxidant effects.
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Pinto, Fabio Henrique Villa. "Avaliação dos efeitos da curcumina sobre a hepatotoxicidade induzida pelo mercúrio em células humanas HepG2." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/60/60134/tde-25092015-144327/.

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O mercúrio é um dos metais mais nocivos presentes no ambiente, advindo tanto de fontes naturais quanto antropogênicas. Os indivíduos estão expostos a diferentes formas do mercúrio através de diversas vias, como a alimentação, principalmente no caso do metilmercúrio presente em peixes. Suas formas orgânicas são muito significativas do ponto de vista toxicológico, considerando-se a exposição da população e seus efeitos pró-oxidantes e genotóxicos envolvidos na origem de inúmeras doenças. Por outro lado, é suposto que compostos polifenólicos e outros antioxidantes da dieta podem exercer atividade protetora contra os efeitos deletérios do mercúrio. A curcumina é um pigmento amarelo polifenólico extraído do rizoma da planta Curcuma longa Linn (Zingiberaceae). Diversas evidências apontam para suas propriedades antioxidantes, de modulação da sinalização celular e alteração da expressão gênica, além da possibilidade de sua utilização na prevenção dos efeitos deletérios dos metais no organismo. Assim sendo, este trabalho teve por objetivo avaliar os efeitos da associação entre o mercúrio e a curcumina, investigando a citotoxicidade de dois compostos orgânicos de mercúrio, metilmercúrio e etilmercúrio, e da curcumina, de forma isolada e combinada, em células HepG2, utilizando o ensaio do MTT. A genotoxicidade desses mesmos compostos também foi avaliada por meio do ensaio do cometa. Além disso, a alteração no estado oxidativo das células pela razão de glutationa (GSH/GSSG) e a alteração na expressão de 84 genes relacionados com vias de dano e reparo no DNA, utilizando-se de PCR-Array, também foram avaliados. Os compostos orgânicos de mercúrio apresentaram citotoxicidade em concentrações iguais ou maiores que 16 ?M. A curcumina apresentou citotoxicidade apenas na concentração de 128 ?M. Nos experimentos de associação entre o mercúrio e a curcumina foi observado um aumento da citotoxicidade, entre a concentração de 8 ?M das duas formas de mercúrio e a concentração de 64 ?M de curcumina. Na avaliação da genotoxicidade foi observado um efeito genotóxico significativo do metilmercúrio nas concentrações de 8, 16 e 32 ?M, enquanto o etilmercúrio apresentou genotoxicidade significativa apenas na concentração de 32 ?M. A curcumina não apresentou genotoxicidade. Na associação dos compostos não foi detectada ação antigenotóxica da curcumina e houve um aumento na genotoxicidade do metilmercúrio em associação com a concentração de 32 ?M de curcumina. A razão de glutationa mostrou um aumento significativo nas células tratadas com metilmercúrio, entretanto isso não foi observado quando o metilmercúrio foi associado com a curcumina. A análise da expressão de 84 genes relacionados com danos no DNA por PCR-Array mostrou alteração na expressão de 26 genes, sendo que 3 deles tiveram aumento na expressão, DDIT3, GADD45A e PPP1R15A, relacionados principalmente com o bloqueio do ciclo celular e o processo de apoptose, e 23 genes tiveram sua expressão reduzida, relacionados com diversas vias de reparo do DNA, checkpoints do ciclo celular e apoptose. Os resultados obtidos indicam que, nas condições avaliadas, a associação da curcumina com o mercúrio aumentou os efeitos deletérios do metal, causando um aumento na citotoxicidade e na genotoxicidade do mercúrio, não se caracterizando como uma possível estratégia de prevenção dos efeitos deletérios do mercúrio
Mercury is one of the most harmful metals present in the environment arising from both natural and anthropogenic sources. The individuals are exposed to different forms of mercury through various sources, such as food, especially in the case of methylmercury in fish, with this organic forms being very significant from a toxicological point of view, considering the exposure of the population and its pro-oxidant and genotoxic effects, involved in the origin of many diseases. On the other hand it is assumed that polyphenolic compounds and other dietary antioxidants can have protective activity against the harmful effects of mercury. Curcumin is a polyphenol extracted from the rhizome of Curcuma longa Linn. (Zingiberaceae). Several evidences show its ability to act as an antioxidant, modulate cell signaling and gene expression, and the possibility of its use in chemoprevention of the deleterious effects of metals. Therefore, this study aimed to evaluate the effects of the association between mercury and curcumin, investigating the cytotoxicity of two organic compounds of mercury, methylmercury and ethylmercury, and curcumin, alone and in combination, in HepG2 cells using the the MTT assay, the genotoxicity of these same compounds through the comet assay, the changes in oxidative state of the cells by the concentration of glutathione and GSH/GSSG ratio and the changes in the expression of 84 genes related to DNA damage anda repair pathways by PCR-Array. Organic mercury compounds showed cytotoxicity at concentrations equal to or greater than 16 uM. Curcumin only showed cytotoxicity at the concentration of 128 ?M. There was an increase in cytotoxicity when mercury (8 ?M) was associated with curcumin (64 ?M). In the genotoxicity assay there was a significant genotoxic of methyl mercury at concentrations of 8, 16 and 32 ?M while ethyl mercury whas genotoxic only at 32 ?M. Curcumin was not genotoxic. There was no anti-genotoxic activity in the association of compounds and there was an increase in genotoxicity of MeHg in association with 32 ?M of curcumin. The quantification of glutathione (GSH/GSSG) showed a significant increase in the GSH/GSSG ratio in cells treated with MeHg, however this was not observed when MeHg was associated with curcumin. Gene expression analysis showed changes in the expression of 26 genes, 3 of them were upregulated, DDIT3, GADD45A and PPP1R15A, mainly related to the cell cycle blockage and apoptosis, and 23 genes were down-regulated, related with DNA repair, cell cycle checkpoints and apoptosis. These results indicate that the combination of curcumin with mercury increased the deleterious effects of the metal, causing an increase in cytotoxicity and genotoxicity of mercury, and do not represent a possible strategy to prevent the harmful effects of mercury.
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20

Fernandes, Carolina da Silva. "Nutrigenómica: da nutrição moderna a Lamark." Master's thesis, [s.n.], 2014. http://hdl.handle.net/10284/4860.

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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
A nutrigenómica estuda o conjunto de alterações que os nutrientes podem causar sobre o genoma humano. Estas alterações podem desencadear diversas alterações no fenótipo expresso, como por exemplo um aumento da propensão para doenças crónicas como a diabetes ou a obesidade. Os estudos nutrigenómicos avaliam também as várias alterações que ocorrem no genoma e epigenoma e como a nutrição pode moldar estas alterações. O ácido fólico tem um importante papel no processo de metilação que ocorre nos vários estágios de crescimento, principalmente durante o desenvolvimento embrionário, prevenindo o desenvolvimento de malformações e o desenvolvimento de várias doenças em idade adulta. As ciências omics contribuem com um conjunto de tecnologias, que permitem desvendar a forma que os nutrientes afetam o genoma ou o epigenoma e como estas alterações afetam cada indivíduo. O conjunto de todas estas ciências permitiram no futuro criar dietas personalizadas que permitiram aumentar a qualidade de vida e a diminuir a propensão para desenvolver diversas doenças crónicas. Nutrigenomics studies the set of changes that nutrients can cause on the human genome. These changes can trigger a number of changes in the expressed phenotype, such as an increased propensity for chronic diseases such as diabetes or obesity. Nutrigenomics studies also evaluate the various changes that occur in the genome and epigenome and how nutrition can shape them. Folic acid plays an important role in the methylation process that occurs in various stages of growth mainly during embryonic development by preventing development defects, and the development of various diseases in adulthood. The omics sciences contribute to a set of technologies, which reveal how nutrients affect the genome and the epigenome and how these changes affect each individual. The set of all these sciences will in the future enable the creation of customized diets that promote an increased quality of life and reduce the propensity for developing various chronic diseases.
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21

Shiyab, Amy S. "Knowledge and Perception of Nutritional Genomics Among Registered Dietitian Nutritionists." Kent State University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=kent1563187321042113.

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22

Alencar, Luciane Luca de. "Estudo dos polimorfismos Pro198Leu no gene da glutationa peroxidase 1 e -617C/A no gene do fator de transcrição Nrf2 com relação ao estresse oxidativo e ao estado nutricional relativo ao selênio de pacientes com diabetes mellitus tipo 1." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/9/9132/tde-27052015-142459/.

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Estudos têm mostrado que a atividade da enzima glutationa peroxidase (GPx) se encontra reduzida na presença do polimorfismo de nucleotideo único (SNP) Pro198Leu no gene que codifica para a GPx1. Associado a isso, polimorfismos na região promotora do gene do fator de transcrição Nrf2, o qual se liga ao elemento de resposta antioxidante na via de expressão de genes de enzimas antioxidantes, também pode alterar a expressão gênica da GPx1. Como o mineral selênio faz parte do sítio catalítico desta enzima antioxidante, muitos estudos têm associado o estado nutricional relativo a este nutriente com doenças relacionadas ao estresse oxidativo, como o diabetes mellitus tipo 1 (DM1). Nesse sentido, este estudo visou avaliar a presença dos SNPs Pro198Leu e -617 C/A no Nrf2, bem como da expressão gênica da GPx1 em pacientes com diabetes mellitus tipo 1 e relacioná-los com marcadores do estado nutricional relativo ao selênio e de estresse oxidativo, comparados com um grupo controle sem a doença. Este é um estudo caso e controle, constituído por dois grupos experimentais, um grupo composto por 77 pacientes com diabetes mellitus tipo 1 (DM1) atendidos no Setor de Endocrinologia do Hospital das Clínicas, com idade entre 10 e 19 anos, de ambos os gêneros, e um grupo controle (GC) constituído por 74 indivíduos da mesma faixa etária, os quais relataram ausência de doenças crônicas. Foi realizada avaliação antropométrica e da ingestão alimentar. Além disso, foram determinados parâmetros bioquímicos de status de selênio, controle glicêmico (glicose sérica, HbA1c), atividade enzimática, concentração de malondialdeído e 8-isoprostanos. A determinação dos SNPs e da expressão gênica foi realizada por PCR em tempo real. O grupo DM1 apresentou média de idade de 15,9 anos e o GC de 13,4 anos. A concentração de glicose sérica e HbA1c foi significativamente diferente entre os grupos (p<0,001). As frequências dos genótipos do SNP da GPx1 para o grupo DM1 e GC foram, respectivamente, 60% e 61% (CC), 30% e 32% (CT), 10% e 7% (TT),estando em equilíbrio gênico. A concentração de selênio no plasma foi significativamente maior no grupo DM1 e, ao avaliar essa concentração de acordo com genótipos, observou-se menor concentração de selênio no plasma no genótipo TT no grupo controle (p<0,05). A expressão gênica da GPx1 não apresentou diferença estatística entre os grupos nem entre os genótipos. O mesmo foi observado quanto à concentração de 8-isoprostanos. No entanto, a atividade das enzimas GPx e SOD assim como a concentração de MDA foram significantemente maiores no grupo DM1 (p<0,05). O estado nutricional de todos participantes em relação ao selênio estava deficiente. Foi observada correlação entre a concentração de selênio no plasma e nos eritrócitos e a atividade da GPx, assim como foi observada maior atividade enzimática e concentração de MDA no grupo DM, sem apresentar diferença na distribuição segundo os alelos estudados. Desta forma, pode-se concluir que independentemente da doença todos os indivíduos apresentaram deficiência de selênio. Em ambos os grupos, foi observada maior peroxidação lipídica, na presença do alelo variante T, o que pode indicar alteração da proteção antioxidante. No entanto, a presença do alelo variante nos SNPs avaliados não apresentaram influencia sobre a expressão gênica.
Studies have shown that the activity of glutathione peroxidase (GPx) is reduced in the presence of single nucleotide polymorphism (SNP) in Pro198Leu encoding GPx1 gene. Beyond that, polymorphism of the transcription factor Nrf2 gene promoter, which binds to the antioxidant response element in the pathway of antioxidant enzymes gene expression, may also alter gene expression of GPx1. As mineral selenium is part of the catalytic site of this antioxidant enzyme, many studies have associated the nutritional status of this nutrient with oxidative stress diseases, such as type 1 diabetes mellitus (DM1). Thus, this study aimed to evaluate the presence of Pro198Leu and -617 C / A in Nrf2 SNPs, as well as GPx1 gene expression in patients with type 1 diabetes mellitus, and to associate them with nutritional status of selenium and stress oxidative markers, comparing with a control group without the disease. This is a case-control study, compound of two groups, one group containing 77 patients with type 1 diabetes mellitus (DM1) from the Service of Endocrinology of Hospital das Clinicas, aged between 10 and 19 years, of both genders, and a control group (CG) was composed for 74 individuals of the same age, who reported no chronic diseases. Anthropometric and dietary intake assessment was performed. In addition, the biochemical parameters of selenium status, glycemic control (serum glucose, HbA1c), enzyme activity, concentration of malondialdehyde and 8-isoprostane were determined. The determination of SNPs and gene expression was performed by real-time PCR. The DM1 group had a mean age of 15.9 years and 13.4 years for the CG. The concentration of serum glucose and HbA 1c were significantly different between groups (p <0.001). The genotype frequencies of the GPx1 SNP for DM1 and control group were, respectively, 60% and 61% (CC), 30% and 32% (CT), 10% and 7% (TT), which is in genetic equilibrium. The selenium concentration in plasma was significantly higher in DM1 group. To assess the selenium concentration according to genotypes, we observed lower plasma concentration in TT genotype in the control group (p <0.05). The GPx1 gene expression showed no statistical difference between groups or between genotypes. The same result was observed for the 8-isoprostane concentration. However, GPx and SOD activity and MDA concentration were significantly higher in DM1 (p <0.05). The nutritional status of all participants in relation to selenium was deficient. Correlation between selenium concentration in plasma and erythrocytes and GPx activity, as well as higher enzyme activity and MDA concentration in the DM1 group were observed, with no significant difference in the distribution according to studied alleles was observed. The presence of the variant allele in the SNPs evaluated showed influence neither on gene expression, nor on the activity of GPx. Thus, it can be concluded that, regardless of the disease, all subjects had low nutritional status of selenium, without genotype influence, and, as expected, oxidative stress was increased in individuals with DM1, as demonstrated by laboratory tests.
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Patricio, Roberta Saraiva Giroto. "Desenvolvimento de material educativo digital para divulgação científica da nutrigenômica." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/9/9132/tde-19102010-161224/.

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Nutrigenômica representa disciplina cientifica recente que surgiu na era do pós-genoma humano, sendo seu foco de estudo a interação gene - nutriente. Profissionais com educação universitária que atuam na área da alimentação e nutrição e da saúde relatam ter dificuldades no entendimento dos princípios dessa disciplina. Recursos digitais como animações representam ferramentas interessantes para o processo de ensino-aprendizagem da nutrigenômica. Dessa forma o objetivo do presente trabalho foi o de desenvolver material educativo digital intitulado \"Fundamentos da Nutrigenômica\", baseado nas animações \"Modulação da expressão gênica por nutrientes e compostos bioativos dos alimentos\" e \"Nutrigenômica e redução do risco de câncer\", para divulgação científica da nutrigenômica para profissionais da área da alimentação e nutrição e da saúde. Para desenvolver o material educativo digital, utilizou-se esquema que se divide nas seguintes etapas: análise e planejamento; modelagem; implementação; avaliação e manutenção. As animações foram produzidas nos programas PowerPoint 2007 e E.M PowerPoint Vídeo Converter. Avaliou-se o material educativo digital por meio de questionário junto a 20 profissionais (nutricionistas, farmacêuticos, engenheiros de alimentos, biólogos, químico, dentista e zootecnista) matriculados ou não em Programas de Pós-Graduação da Universidade de São Paulo nas áreas da alimentação e nutrição e da saúde. Mais de 80% dos participantes concordaram fortemente ou concordaram com as seguintes afirmações: \"O material educativo digital é de fácil manuseio\"; \"A utilização desse tipo de recurso tem vantagens sobre textos\"; \"O material educativo digital trouxe conhecimentos novos sobre Nutrigenômica\"; \"Os conceitos estão expostos de forma clara\"; \"Meus conhecimentos anteriores foram suficientes para aprender com o material educativo digital\"; \"Os textos estão redigidos com clareza\"; \"As animações auxiliam a compreender os fenômenos exibidos\"; \"Aprendi bastante sobre os fundamentos da nutrigenômica com o material educativo digital\". Conclui-se que o material educativo digital \"Fundamentos da nutrigenômica\" representa ferramenta útil para divulgação científica da nutrigenômica junto a profissionais da área da alimentação e nutrição e da saúde.
Nutrigenomics represents recent scientific discipline that has emerged in the post-human genome era, with focus on gene - nutrient interaction. Professionals with university education working in the field of food and nutrition and health report having difficulties in understanding the principles of this discipline. Digital resources such as animations represent interesting tools for the teaching and learning of nutrigenomics. Thus the objective of this study was to develop digital learning material entitled \"Fundamentals of Nutrigenomics\", based on the animations \"Modulation of gene expression by nutrients and bioactive food compounds\" and \"Nutrigenomics and risk reduction of cancer,\" for scientific dissemination of nutrigenomics for professionals in the food and nutrition and health areas. To develop the digital learning material, we used the scheme that is comprised by the following steps: analysis and planning, modeling, implementation, evaluation and maintenance. The animations were produced with the PowerPoint 2007 and EM Video Converter softwares. We evaluated the digital educational materials through a questionnaire provided to 20 professionals (nutritionists, pharmacists, food engineers, biologists, chemist, dentist and zootechnist) registered or not in Graduate Programs from University of Sao Paulo in the areas of food and nutrition and health. Over 80% of participants strongly agreed or agreed with the following statements: \"The digital educational material is easy to handle\", \"The use of this resource type presents advantages over text\", \"The digital learning material brought new knowledge on Nutrigenomics\" , \"The concepts are clearly exposed\", \"My previous knowledge was sufficient to learn from the digital learning material\", \"The texts are written with clarity\", \"The animations help to understand the exhibited phenomena\", \"I learned a lot about nutrigenomics fundamentals with the digital learning materials\". We conclude that the digital learning material \"Fundamentals of Nutrigenomics\" represents a useful tool for scientific dissemination of nutrigenomics for professionals in the field of food and nutrition and health.
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Almeida, Danielle Fontes de. "Avaliação do perfil de expressão gênica de linhagens celulares do tecido mamário com diferentes níveis de expressão do receptor HER-2 tratadas com ácido docosahexaenoico." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-08082013-092359/.

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O câncer de mama permanece como segundo tipo de câncer mais frequente no mundo e o primeiro entre as mulheres. Tumores de mama podem ser categorizados pela expressão de receptores como o HER-2 (receptor de fator de crescimento epidermal 2). A hiperexpressão do receptor HER-2 é observada em cerca de 30% dos carcinomas de mama, e está associada a prognósticos desfavoráveis. Os ácidos graxos poli-insaturados (AGPI) , como os ácidos graxos ômega-3, parecem diminuir o risco de câncer de mama. O ácido docosahexaenoico (DHA), um tipo de AGPI ômega-3 parece ter o maior potencial antitumoral no câncer de mama. Alguns mecanismos de ação foram propostos para a ação do DHA no controle do câncer de mama, no entanto, faltam dados para elucidar os mecanismos moleculares do DHA no tecido mamário normal e cancerígeno. Dessa maneira, o objetivo desse trabalho foi avaliar a ação do DHA na modulação da expressão de genes em linhagem celular normal (HB4a), transformada (HB4aC5.2) e de carcinoma mamário humano (SKBR-3). As linhagens estudadas foram tratadas com 100 ?M de DHA ou controle (etanol) durante 72 horas. Após a extração de RNA realizamos a técnica de expressão gênica global (Microarray) para encontrar os genes diferencialmente expressos, em relação ao tratamento com DHA, em cada linhagem celular estudada. Na linhagem normal (HB4a) observamos 174 genes diferencialmente expressos (p<0,01), sendo 136 hiperexpressos e 38 hipoexpressos, na linhagem celular transformada (HB4aC5.2) encontramos 208 genes diferencialmente expressos (p<0,01), sendo 32 hiperexpressos e 176 hipoexpressos. A linhagem do carcinoma mamário (SKBR-3) apresentou 126 genes diferencialmente expressos (p<0,01), sendo 48 hiperexpressos e 78 hipoexpressos. A análise ontológica destes genes permitiu identificar processos biológicos como: adesão celular, diferenciação celular e metabolismo lipídico. Concluímos que o DHA altera o perfil de expressão gênica de maneiras distintas em linhagem normal, transformada e de carcinoma mamário humano. Além disso, encontramos após o tratamento com DHA genes envolvidos com o metabolismo lipídico nas linhagens que hiperexpressam o receptor HER-2
Breast cancer remains the second most common cancer in the world and first among women. Breast tumors can be categorized by the expression of receptors such as HER-2. Overexpression of HER-2 receptor is associated with unfavorable prognosis.The polyunsaturated fatty acids (PUFAs) omega- 3 appears to decrease the risk of breast cancer. Docosahexaenoic acid (DHA), a type of omega-3 PUFAs, seems to have greater antitumor potential in breast cancer. However, the gene expression profile resulting from the action of DHA in breast cancer has not been elucidated yet. We aimed to examine the effects of DHA on normal breast cell line (HB4a), transformed cell line (HB4aC5.2) and breast cancer cell line (SKBR-3) and using a microarray approach. Cells were treated with 100?M of DHA for 72 hours. We identified 174, 208 and 126 differentially expressed genes after DHA treatment, in HB4a, HB4aC5.2 and SKBR3, respectively. Notably, the molecular pathways for the differentially expressed genes included those related to lipid metabolism, cell growth, molecular transport and cell-to-cell signaling. Where found genes related to overexpression of HER-2 after treatment with DHA. These genes involved in lipid metabolism and were down-expressed after treatment, suggesting a possible mechanism DHA in breast cancer by lipid metabolism control
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Oleaga, Sancho Carlota. "Estudio nutrigenómico de compuestos polifenólicos del cacao y del café en células tumorales humanas." Doctoral thesis, Universitat de Barcelona, 2012. http://hdl.handle.net/10803/96129.

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La investigación en genómica nutricional combina las áreas de conocimiento de biología molecular, genética y nutrición. Los compuestos bioactivos de la dieta se podrían definir como aquellos componentes con potencial para modificar un elevado número de procesos biológicos asociados al equilibrio entre salud y enfermedad. En la presente tesis se han desarrollado tres estudios nutrigenómicos con compuestos polifenólicos del cacao y del café, con el objetivo de profundizar en el conocimiento de los mecanismos de acción por los que ejercen su actividad. En el estudio de los efectos de un extracto de polifenoles de cacao (PCE) en líneas celulares de cáncer de mama, las conclusiones obtenidas son las siguientes: 1. El tratamiento con PCE induce la expresión de CYP1A1, así como sus niveles de proteína y la actividad enzimática en dos líneas celulares de cáncer de mama, MCF-7 y SKBR3. 2. La inducción de CYP1A1 mediada por PCE tiene lugar a través de la vía de señalización de AhR. PCE induce la transcripción de CYP1A1 a través de la unión de AhR a las cajas XRE de su promotor en ambas líneas celulares. 3. PCE induce los niveles de ERα en la línea celular SKBR3 aumentando la síntesis de la proteína, pero su vida media se reduce aproximadamente 10 horas en comparación con la proteína basal. 4. La incubación con PCE y tamoxifeno (TAM) a concentraciones no citotóxicas inducen un efecto sinérgico provocando un descenso en la viabilidad de dos líneas de cáncer de mama, MCF-7 y SKBR3, pero no en la línea no tumoral HEK293T. En el análisis de los efectos de distintos metabolitos del cacao sobre la expresión de la apolipoproteína A1 en la línea celular HepG2 de hepatoma, establecimos las siguientes conclusiones: 1. La epicatequina (EPI) y los metabolitos del cacao inducen la expresión de ApoAI en la línea celular HepG2. 2. El tratamiento con EPI en células HepG2 induce la unión de factores de transcripción a dos regiones del “liver specific enhancer”, Site A y Site B. En la unión a Site A participan los factores de transcripción HNF-4, RXRα y ERα, además de HNF3β de manera indirecta. En la unión a Site B participa el factor de HNF-3β. EPI y los metabolitos del cacao estudiados inducen los niveles de mRNA de HNF-3β. 3. La transcripción de ApoAI se induce por EPI y los metabolitos del cacao estudiados a través del Site B, siendo 3-M-EPI el metabolito que provoca una mayor activación transcripcional. 4. Los factores de transcripción NFY y Sp1, además de HNF-3β, participan en la unión al Site B inducida por la incubación con 3-M-EPI. La sobreexpresión de NFY y Sp1 induce la transcripción de ApoAI a través del Site B. Finalmente en la aproximación transcriptómica en células de cáncer de colon tratadas con ácido cafeico y café soluble, podemos concluir que: 1. El tratamiento con ácido cafeico (CA) y con café (ICC) genera un cambio en el perfil de expresión de la línea tumoral HT29. 2. Se han identificado dos genes nodo, STAT5B y ATF-2, tras la generación de una red de asociación biológica a partir de los genes diferencialmente expresados comunes a ambos tratamientos, CA e ICC. 3. La validación de los cambios en la expresión de ambos genes confirma la sobreexpresión de STAT5B e infraexpresión de ATF-2 inducida por la exposición a CA e ICC. También se ha confirmado el aumento en la proteína STAT5B inducida por el tratamiento con CA y con ICC y la disminución de los niveles de ATF-2 debidos al tratamiento con CA. 4. El tratamiento con CA e ICC modula los niveles de ciclina D1, proteína regulada por STAT5B y ATF-2 en dos líneas celulares de cáncer. En HT29, la exposición a CA reduce los niveles de ciclina D1, mientras que ICC induce los niveles de ciclina D1 al igual que los de ATF-2. En MCF-7 ambos tratamientos, CA e ICC, consiguen una disminución drástica de los niveles de proteína ciclina D1, a pesar de no acompañarles la disminución de ATF-2.
NUTRIGENOMIC STUDIES OF COCOA AND COFFEE POLYPHENOLS IN HUMAN TUMOR CELL LINES Nutritional genomics research combines the knowledge areas of molecular biology, genetics and nutrition. Nutrigenomics studies how diet, or compounds from diet are able to modulate gene expression. Diet compounds such as polyphenols are known to produce beneficial effects in human homeostasis. Cocoa and coffee are two polyphenol food sources well studied in nutritional research. The aim of this work was to get further insight in the understanding of the mechanism of action through which cocoa and coffee polyphenols exert their beneficial effect, using three different nutrigenomics approaches. The main conclusions of these nutrigenomic studies are: 1) The interaction between ERα and AhR upon incubation with a polyphenolic cocoa extract leads to CYP1A1 induction in breast cancer cells. The synergy between PCE and non-cytotoxic tamoxifen concentrations opens the possibility for a combination therapy based on polyphenols from cocoa that increased tamoxifen efficacy. 2) The activation of Apolipoprotein AI transcription through Site B in its promoter by cocoa flavanol metabolites is mainly mediated by an increase in HNF-3β, with a significant contribution of Sp1 and NFY, as a mechanism for the protective role of these compounds in cardiovascular diseases. 3) Coffee polyphenols are able to affect cyclin D1 expression in cancer cells through the modulation of STAT5B and ATF-2. The results of this thesis led to three publications in international journals; i) “CYP1A1 is overexpressed upon incubation of breast cancer cells with a polyphenolic cocoa extract” in European Journal of Nutrition ii) “Cocoa flavanol metabolites activate HNF-3β, Sp1 and NFY mediated transcription of Apolipoprotein AI in human cells” in Molecular Nutrition and Food Research iii) “Coffee Polyphenols Change the Expression of STAT5B and ATF-2 Modifying Cyclin D1 Levels in Cancer Cells” in Oxidative Medicine and Cellular Longevity.
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Konstantinidou, Valentini. "Molecular mechanisms involved in the protective effect of Mediterranean diet and olive oil consumption in humans." Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/7208.

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The scope of the present work was to investigate whether the protective role of the traditional Mediterranean diet (TMD), and virgin olive oil (VOO) rich in phenolic compounds (PC), towards cardiovascular disease can be mediated through gene expression changes. Two trials were performed to assess the in vivo nutrigenomic effects of TMD and VOO in healthy volunteers. The results point out: a) significant gene expression changes of those genes related with cardiovascular-risk processes after VOO ingestion; b) a down-regulation in the expression of atherosclerosis-related genes after a 3-month intervention with a TMD; and c) an olive oil PC health-protective nutrigenomic effect within the frame of the TMD. Changes in gene expression were concomitant with decreases in oxidative damage and systemic inflammation markers. Data from our studies provide further evidence to recommend both the TMD and the VOO as a useful tool for the prevention of atherosclerosis.
El objetivo de este estudio es investigar si el papel protector de la dieta Mediterránea tradicional (TMD) y del aceite de oliva virgen (VOO), rico en compuestos fenólicos (PC), puede ser mediado a través de cambios en la expresión génica. Se realizaron dos ensayos clínicos para evaluar los efectos nutrigenómicos de la TMD y del VOO, in vivo, en voluntarios sanos. Los resultados mostraron a) cambios en la expresión génica de genes relacionados con el riesgo cardiovascular tras la ingestión del aceite virgen de oliva, b) una infra-expresión en la expresión de genes relacionados con el proceso aterosclerótico tras una intervención con TMD de 3 meses y c) que los compuestos fenólicos del aceite de oliva ejercen un efecto nutrigenómico protector en el marco de la TMD. Los cambios en la expresión génica fueron coherentes.
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Castro, Rita de Cássia Borges de. "Efeito do ácido docosahexaenoico (DHA) sobre eventos epigenéticos em diferentes linhagens de câncer de mama." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-03102013-094648/.

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Alterações epigenéticas, como metilação do DNA e modificações pós traducionais em histonas, tem importante papel na carcinogênese mamária. A modulação de eventos epigenéticos constitui relevante alvo terapêutico, devido ao seu caráter reversível. Experimentalmente, o ácido docosahexaenoico (DHA), um membro da família dos ácidos graxos ômega-3, é capaz de diminuir proliferação, induzir morte celular e diminuir o potencial invasivo de células tumorais de mama. No entanto, os mecanismos antitumorais do DHA e sua capacidade de modular eventos epigenéticos ainda não estão totalmente elucidados. Nosso objetivo foi verificar, in vitro, a ação do DHA em eventos epigenéticos em diferentes linhagens de carcinoma mamário humano. Três linhagens celulares de câncer de mama (MDA-MB-231, SKBR-3 e MCF-7) foram tratadas durante 72 horas com 100 ?M de DHA ou etanol (controle). As modificações pós traducionais em histonas, acetilação no resíduo de lisina 9 da histona 3 (H3K9ac) e no resíduo 16 da histona 4 (H4K16ac), bem como trimetilação no resíduo de lisina 9 da histona 3 (H3K9me3) e no resíduo de lisina 27 da histona 3 (H3K27me3) foram avaliadas pela técnica de western blot. A análise da expressão do genes RASSF1A, DNMT1, DNMT3A e DNMT3B foi feita pela técnica da reação em cadeia da polimerase quantitativa via transcriptase reversa (RT-qPCR). A avaliação do padrão de metilação de região promotora do gene RASSF1A foi realizada pela técnica de reação em cadeia da polimerase metilação específica (MS-PCR). Foram também analisadas as fases do ciclo celular por citometria de fluxo. Comparado ao controle, o DHA induziu a acetilação no resíduo 16 da histona 4 (H4K16ac) nas linhagens MCF7 (p = 0,04) e MDA-MB-231 (p = 0,03). Observamos que a H3K9me3 foi parcialmente inibida nas linhagens MDA-MB-231 e SKBR-3, após o tratamento com DHA, mas sem alcançar valor estatisticamente significante. Encontramos também diminuição dos níveis de H3K27me3 após o tratamento com DHA nas três linhagens estudadas, porém não foi estatisticamente significativo. O DHA aumentou a expressão do gene RASSF1A na linhagem MCF-7 (1,98 vezes, p = 0,03), mas não nas linhagens MDA-MB-231 e SKBR-3. Não houve mudanças estatisticamente significativas na expressão dos genes DNMT1, DNMT3A e DNMT3B. As análises qualitativas da metilação demonstraram que a região promotora analisada do gene RASSF1A apresentou-se hipermetilada nas três linhagens celulares. Após o tratamento com DHA, houve tendência de desmetilação na região promotora do RASSF1A na linhagem MCF-7 e SKBR3, mas não na linhagem MDA-MB-231. Não houve diferença significativa na porcentagem de morte e distribuição das células MDA-MB-231, SKBR-3 e MCF-7 nas diferentes fases do ciclo celular após tratamento com DHA. Em conclusão, o DHA pode atuar em mecanismos epigenéticos e, ainda, reativar o gene supressor de tumor, como RASSF1A, anteriormente silenciado por hipermetilação, em células MCF-7. Espera-se que esses resultados contribuam para melhor compreensão do potencial papel anticâncer do DHA no câncer de mama
Epigenetic changes, such as DNA methylation and post-translational histone modifications, play an important role in mammary tumorigenesis. Epigenetic events are important as therapeutic targets, because of its reversible nature. Experimentally, docosahexaenoic acid (DHA), a member of the omega-3 fatty acids family, can reduce proliferation, induce apoptosis and decrease the invasive potential of breast tumor cells. However, the antitumor mechanism of DHA and its ability to modulate epigenetic events are not completely understood. Our objective was to verify, in vitro, the action of DHA in epigenetic events related to transcriptional reactivation of tumor suppressor gene, such as RASSF1A, in different human breast cancer cell lines. Three breast cancer cell lines (MCF-7, MDA-MB-231, SKBR-3) were treated with DHA (100 ?M) or vehicle (ethanol) for 72 hours. Western blot was used to analyze histone modification, as histone H3 lysine 9 (H3K9ac) and histone H4 lysine 16 (H4K16ac) acetylation, H3K9 trimethylation (H3K9me3) and H3K27 trimethylation (H3K27me3). Real time quantitative PCR (RT-qPCR) was performed for gene expression quantification of RASSF1A, DNMT1, DNMT3A and DNMT3B. DNA methylation of the promoter region of RASSF1A was evaluated by methylation specific PCR (MS-PCR). Moreover, we evaluated the phases of the cell cycle by flow cytometry. Compared to control cells, DHA induced H4K16ac in MCF-7 (p=0.04) and MDA-MB-231 (p=0.03). We observed that H3K9me3 was partially inhibited in MDA-MB-231 and SKBR-3 cells, after treatment with DHA, but did not reach a statistically significant value. We also found decreased levels of H3K27me3 after treatment with DHA in the three cell lines studied, but not statistically significant. DHA increased RASSF1A expression on MCF-7 (1.98 fold; p=0.03), but not in MDA-MB-231 and in SKBR-3 cells. There were no statistically significant changes in expression of genes DNMT1, DNMT3A and DNMT3B. These three breast cancer cells lines show methylation in specific region of RASSF1A promoter. DHA treatment increased RASSF1A promoter region hypomethylation in MCF-7 and SKBR-3. No significant difference was observed in the percentage of cell death nor cell distribution of MDA-MB-231, SKBR-3 and MCF-7 at different stages of the cell cycle after treatment with DHA. In conclusion, we suggest that DHA may act beneficially in epigenetic mechanisms and reactivation of tumor suppressor gene, RASSF1A as previously silenced by hypermethylation. It is hoped that these results can contribute to better understanding of the anticancer role of DHA in breast cancer
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Fontaine-Bisson, Benedicte. "Nutrigenomics, inflammation and biomarkers of cardiovascular disease." 2008. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=742613&T=F.

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29

Furness, Denise Lyndal Fleur. "Genome damage and folate nutrigenomics in uteroplacental insufficiency." 2007. http://hdl.handle.net/2440/57508.

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Pregnancy complications associated with placental development affect approximately one third of all human pregnancies. Genome health is essential for placental and fetal development, as DNA damage can lead to pregnancy loss and developmental defects. During this developmental phase rapid DNA replication provides an increased opportunity for genome and epigenome damage to occur[1]. Maternal nutrition is one of the principal environmental factors supporting the high rate of cell proliferation and differentiation. Folate functions in one-carbon metabolism and regulates DNA synthesis, DNA repair and gene expression[1]. Deficiencies or defects in gene-nutrient interactions associated with one-carbon metabolism can lead to inhibition of cell division, cell cycle delay and an excessive apoptotic or necrotic cell death rate [2], which may affect placentation. This study is the first to investigate the association between genomic damage biomarkers in late pregnancy complications associated with uteroplacental insufficiency (UPI) including preeclampsia and intrauterine growth restriction (IUGR). The results indicate that genome damage in the form of micronucleated cells in peripheral blood lymphocytes at 20 weeks gestation is significantly increased in women at risk of developing an adverse pregnancy outcome. The observed OR for the high micronuclei frequency may be the highest observed for any biomarker selected in relation to risk of pregnancy complications to date (15.6 – 33.0). In addition, reduced apoptosis was observed in association with increased micronuclei, suggesting that the cells may have escaped specific cell-cycle checkpoints allowing a cell with DNA damage to proceed through mitosis. This study demonstrated that an increase in plasma homocysteine concentration at 20 weeks gestation is associated prospectively with the subsequent development of UPI, indicating a causal relationship. The MTR 2756 GG genotype was significantly associated with increased plasma homocysteine concentration and UPI. Furthermore, the MTHFD1 1958 single nucleotide polymorphism was associated with increased risk for IUGR.
http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1309296
Thesis (Ph.D.) -- School of Paediatrics and Reproductive Health, 2007
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30

Krupková, Lucie. "Nutrigenetické a nutrigenomické aspekty u vybraných patologií." Master's thesis, 2010. http://www.nusl.cz/ntk/nusl-279562.

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DIPLOMA THESIS Nutrigenetic and nutrigenomic aspects at selected pathological states. Mentor of Diploma Thesis: PharmDr. Miloslav Hronek, Ph.D. Lucie Krupková, 2010 Abstract The effect of nutrition to human health is undisputable. Certain dietary compounds can influence each of us in different ways. Although people have almost identical genome, there are imperceptible diffenrences that make us unique. This uniqueness is shown in different responses to specific nutrients. The matter of diet, genes and gen-diet interactions are solved by two developing scientific disciplines - nutrigenomics and nutrigenetics. Nutrigenomics aims to determine the influence of common dietary ingredients on the genome, and attempts to relate the resulting different phenotypes to differences in the cellular and genetic response of the biological system. Nutrigenetics identifies and characterizes gene variants associated with differential responses to nutrients, and relates these variants to disease states. Scientific research is focused primarily on chronic diseases including obesity, cardiovascular diseases, diabetes mellitus type 2 and cancer. The onset of the diseases is caused by enviromental factors on the one hand, and by individual's genotype on the other hand. Nutrigenetics searches for candidates' genes whose...
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31

Wong, Monica. "Cluster Analyses to Assess Weight Loss Maintenance: An Application of Clustering in Nutrigenomics." Thesis, 2011. http://hdl.handle.net/10214/2860.

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Within nutrigenomics, clustering using data generated by microarray gene expression profiles can be used to identify sub-populations of subjects that respond differently to a given diet intervention. The use of clustering analyses is promising in obesity-related research as personalized nutrition is gaining popularity. This thesis focuses on clustering a human subcutaneous adipose tissue gene expression data set obtained during a low-calorie diet intervention to aid in the prediction of 6-month weight loss maintenance. The aims of the study were (1) to identify the best performing clustering method for clustering samples, (2) to identify differential responders to the low-calorie diet, and (3) to identify the biological pathways affected during the low-calorie diet by weight maintainers and weight regainers. MCLUST performed the best when clustering samples using relative weight change and either fasting insulin or insulin resistance change. Furthermore, it identified differences in the regulation of pathways between weight maintainers and regainers.
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32

Abrahams, Mariëtte, L. J. Frewer, Eleanor J. Bryant, and Barbara Stewart-Knox. "Perceptions and experiences of early-adopting registered dietitians in integrating nutrigenomics into practice." 2017. http://hdl.handle.net/10454/13480.

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yes
Purpose - This research explores the perceptions and experiences of early adopters of the technology. Design/Method/Approach - Registered Dietitians (RD´s) (N=14) were recruited from the UK, Canada, South-Africa, Australia, Mexico and Israel. Six qualitative interviews and two focus groups were conducted online using a conference calling platform. Data were recorded, transcribed and thematically analysed. Findings - Early adopters of Nutrigenomics (NGx) were experienced, self-efficacious RD’s who actively sought knowledge of NGx through communication with one another and the broader scientific community. They considered NGx an extension of current practice and believed RD’s had the skills to deliver it. Perceived barriers to widening the application of NGx were linked to skepticism among the wider dietetics community. Proliferation of unregulated websites offering tests and diets was considered ‘pseudoscience’ and detrimental to dietetics fully embracing NGx. The lack of a sustainable public health model for the delivery of NGx was also perceived to hinder progress. Results are discussed with reference to ‘diffusion of innovation theory’. Originality/Value - The views of RD’s who practice NGx have not been previously studied. These data highlight requirements for future dietetic training provision and more inclusive service delivery models. Regulation of NGx services and formal recognition by professional bodies is needed to address the research/practice translation gap.
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33

Yeh, Chi-Tai, and 葉淇臺. "Nutrigenomics approach to understanding the role of dietary phenolic acids in sulfate conjugation." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/51303625552550282285.

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博士
國立中興大學
食品科學系
93
Abstract Sulfation (sulfonation) is one of the major phase II conjugative reactions involved in the biotransformation of various endogenous compounds, drugs, and xenobiotics as well as in steroid biosynthesis, catecholamine metabolism, and thyroid hormone homeostasis. Phenolic acids such as hydroxybenzoic acids and hydroxycinnamic acids are antioxidant compounds in fruits and vegetables. Research on phenolic acids is of current interest due to the important biological and pharmacological properties attributed to their antioxidant properties. Therefore, the objective of this study was to investigate the effect of dietary polyphenolic compounds on human sulfotransferase. There are six topics included in this study: (1) Effect of phenolic Acid on human phenolsulfotransferases in relation to their antioxidant activity (2) Synergistic effect of antioxidant phenolic acids on human phenolsulfotransferase activity (3) Effect of vegetables on human phenolsulfotransferases in relation to their antioxidant activity and total phenolics (4) Induction of phenolsulfotransferase expression by antioxidant phenolic acids in human hepatoma HepG2 cells (5) Modulation of hepatic phase II phenolsulfotransferase and antioxidant status by phenolic acids in rats. (6) Cytoprotective effects of P-form phenolsulfotransferase induction by phenolic acid Our studies revealed that (1) p-hydroxybenzoic acid, gallic acid, gentisic acid, ferulic acid, and p-coumaric acid all could increase the activities of both PST-P and PST-M. These phenolic acids also possessed antioxidant capacity in the ORAC and TEAC assays. (2) Furthermore, in both two-compound and three-compound combinations with each of other phenolic acids, gallic acid and gentistic acid exhibit the potential synergistic effects in the promotion of PSTs activities. The overall effects of phenolic acids on the activities of PST-P and PST-M are highly correlated to their ORAC values, suggesting that antioxidant phenolic acids might alter sulfate conjugation. (3) Moreover, the PST-P activity was significantly induced by asparagus, broccoli, cauliflower, celery, and eggplant, whereas PST-M activity was induced by asparagus, broccoli, carrot, eggplant, and potato at a concentration of 100 g/ml. The major polyphenols in broccoli, the most potential inducer in both forms of PSTs activities, was antioxidant phenolic acids. HPLC retention times and standard spiked indicated the presence of gallic acid, p-hydroxybenzoic acid, p-coumaric acid, gentisic acid, and ferulic acid in broccoli. These results imply that vegetables have a capability of inducing PST activity, and the PST induction may be possibly ascribed to antioxidant phenolic acids in vegetable extracts. (4) Furthermore, human hepatoma cell line HepG2 was used as a model to investigate the effect of antioxidant phenolic acids on enzymatic activity and expression of one of the major phase II sulfateconjugation enzymes, PST-P. The results showed that gallic acid, gentisic acid, p-hydroxybenzoic acid, and p-coumaric acid were found to increase the PST-P activity in a dose-dependent manner. A significant correlation between the expressions of PST-P mRNA and the corresponding PST-P activity was observed. The results demonstrated that certain antioxidant phenolic acids could induce PST-P activity in HepG2 cells by promoting PST-P mRNA and protein expression, suggesting a novel mechanism by which antioxidant phenolic acids may be implicated in phase II sulfate conjugation. (5) Used the animal models to investigate the the modulatory effect of phenolic acids on hepatic phase II phenolsulfotrnasferases and antioxidant status in vivo. According to the results, phenolic acids in dosage of 100 mg/body weight significantly increased PST-P and PST-M activities as compared with the that of the control rats (p<0.05). Reverse transcription polymerase chain reaction results indicated that the changes in PST-P and PST-M mRNA levels by phenolic acids were similar to those noted in the enzymes activity levels. The plasma obtained form phenolic acids-administrated rats were significantly increased the oxygen radical absorbance capacity (ORAC) values than that form control rats. In a bioavailability study, following oral administration of gallic acid and p-coumaric acid (100 mg/kg body weight), the phenolic acid were detected in the plasma and the Cmax values after 2.0 h administration were 665±23, and 550±33 nmol/L, respectively. There was a significant correlation between the activity of both forms of PSTs and the antioxidant capacity of ORAC value by phenolic acids, suggesting that phenolic acids might alter sulfate conjugation and antioxidant capacity in living systems. (6) Nrf2 can initiate transcription of many antioxidant response element (ARE) mediated antioxidant genes expression. In this study, it was found that antioxidant phenolic acids could induce translocation of cytoplasmic Nrf2 into nucleus and JNK/p38 MAPK signaling cascade was involved in this process. It was demonstrated that antioxidant phenolic acids could remarkably induce PST-P protein expression and this induction of PST-P by antioxidant phenolic acids could be inhibited by p38 MAPK inhibitor SB203580. Taken together, we speculate that antoxidant phenolic acids activate translocation of Nrf2 into nucleus through JNK/p38 MAPK. Nrf2 then binds to the regulatory transcription region of PST gene in the nucleus and initiates gene transcription that results in final expression of chemoprotective PST-P protein. Our results provide better understanding of the effects of phenolic acids on human PST activities, as well as information regarding the intake of phenolic antioxidant for human health. Keywords: Platelet, human phenolsulfotransferases, phenolic acids, antioxidant activity, Synergistic effect, Cytoprotective, Signal transduction, antioxidant responsive element
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34

Su, Hsiang-Ling, and 蘇香綾. "Exploring the Consumer Acceptance Of and Preferences In Nutrigenomics-Based Personalized Health Management Service." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/86914301908026322071.

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碩士
國立中興大學
科技管理研究所
100
Nutrigenomics is an emerging technology that offers opportunities for personalized health management from the preventive and promoting perspectives. Despite general agreement on the value of nutrigenomics as a powerful approach to unravel the complex diet-health relationships, challenges in applications at the scientific, regulative, and ethical levels have also been widely discussed. However, research into the consumer acceptance and potential service models of such application is relatively scarce. As the awareness and demand for preventive medicine continues to grow worldwide along with the ever increasing market of health optimizing improving product and service, the successful development of such innovative applications would require better knowledge from consumer''s perspectives. The research objectives of the current study is 1) To understand the consumer perception of Nutrigenomics based personalized health management and identify the factors that affect the consumer acceptance; 2) To explore the consumer preference in developing the service model in personalized health management particularly in the Asian population. A comprehensive multimedia online survey was carried out to understand the consumer acceptance of nutrigenomics based personalized health management and to explore the consumer preferences of related service. Moreover, the willingness of service adoption when offered with preferred service model was also investigated. The results of the current study demonstrated an extraordinary high level of acceptance and willingness when consumer’s preferences are met. In accordance to previous finding, perceived benefit was found to be the most critical factor in consumer acceptance while other suggested factors remained insignificant. While most of the emerging services in Asia followed the American and European models, the results of current survey showed misalignment of available services and consumer preferences. According to the findings of the current study, a service delivery model based on the consumer’s preference is proposed with regards of government intervention. In summary, the current study provides early insight in the development of personalized health management services in Asian countries.
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35

Eny, Karen M. "Genetic Determinants of Carbohydrate Consumption." Thesis, 2010. http://hdl.handle.net/1807/26147.

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Background: There are a number of biological pathways that affect our ingestive behaviours, including energy homeostasis, food reward, and taste. Given that carbohydrates such as sugars, provide energy and a sweet taste, examining candidate genes in each pathway may help explain differences in carbohydrate consumption behaviours. Objective: To determine whether variations in genes encoding a glucose transporter (GLUT2), a dopamine receptor (DRD2), and sweet taste receptor (TAS1R2) are associated with differences in sugar consumption in two distinct populations. Methods: Population 1 included diabetes-free young adults where dietary intake was assessed using a one month 196-item food frequency questionnaire (FFQ). Population 2 consisted of individuals with type 2 diabetes. Dietary intake was assessed using 3-day food records administered 2 weeks apart; food record 1 (FR1) and 2 (FR2). Subjects were genotyped for the Thr110Ile variation in GLUT2 (n1=587; n2=100), the C957T variation in DRD2 (n1=313; n2=100), and the Ser9Cys and Ile191Val variations in TAS1R2 (n1=1037; n2=100) using real-time PCR. Results: In comparison to individuals homozygous for the GLUT2 Thr allele, consumption of sugars was higher among Ile carriers in population 1 (133 ± 5 vs 118 ± 3 g/d, p=0.006) and population 2 on two separate food records (FR1: 112 ± 9 vs 87 ± 5 g/d, p=0.02; FR2: 105 ± 8 vs 78 ± 4 g/d, p=0.002). For the C957T variation in population 1, we detected a significant DRD2xSex interaction with the consumption of sucrose decreasing with each T allele among men (p=0.03) and a heterosis mode of inheritance among women where heterozygotes consumed the most (p=0.01). For TAS1R2, we detected a significant TAS1R2xBMI interaction and among overweight individuals, carriers of the Val allele consumed less sugars than those with the Ile/Ile genotype (103 ± 6 vs122 ± 6 g/d, p=0.01). In population 2, carriers of the Val allele consumed less sugars than individuals with the Ile/Ile genotype (83 ± 6 vs 99 ± 6 g/d, p=0.04) on FR2. Conclusions: Our findings demonstrate that genetic variation in GLUT2, DRD2 and TAS1R2 affect habitual sugar consumption and suggest that selection of dietary sugars can be influenced by different biological pathways.
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36

Asik, Christine Rose. "Genetic Variation in Bitter Taste Perception, Food Preference and Dietary Intake." Thesis, 2010. http://hdl.handle.net/1807/32204.

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The role of variation in the TAS2R50 bitter taste receptor gene is unknown, but may influence taste perception and dietary habits. Individuals (n=1171) aged 20 to 29, from the Toronto Nutrigenomics and Health Study, completed a food preference checklist and a semi-quantitative food frequency questionnaire to assess their preference and intake of potentially bitter foods and beverages. DNA was isolated from blood and genotyped for 3 polymorphisms in the TAS2R50 gene (rs2900554 A>C; rs10772397 A>G; rs1376251 A>G). Taste intensity was examined using taste strips infused with 3µg of naringin. The rs2900554 SNP was associated with naringin taste intensity, grapefruit preference and grapefruit intake in females. Homozygotes for the C allele reported the highest frequency of experiencing a high naringin taste intensity, disliking grapefruit and not consuming grapefruit. The rs10772397 and rs1376251 SNPs were associated with disliking grapefruit. These results suggest that naringin may be a ligand for the T2R50 receptor.
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37

Stewart-Knox, Barbara, Jerko Markovina, A. Rankin, B. P. Bunting, S. Kuznesof, A. R. H. Fischer, der Lans I. A. van, et al. "Making personalised nutrition the easy choice: creating policies to break down the barriers and reap the benefits." 2016. http://hdl.handle.net/10454/8904.

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Yes
Personalised diets based on people’s existing food choices, and/or phenotypic, and/or genetic information hold potential to improve public dietary-related health. The aim of this analysis, therefore, has been to examine the degree to which factors which determine uptake of personalised nutrition vary between EU countries to better target policies to encourage uptake, and optimise the health benefits of personalised nutrition technology. A questionnaire developed from previous qualitative research was used to survey nationally representative samples from 9 EU countries (N = 9381). Perceived barriers to the uptake of personalised nutrition comprised three factors (data protection; the eating context; and, societal acceptance). Trust in sources of information comprised four factors (commerce and media; practitioners; government; family and, friends). Benefits comprised a single factor. Analysis of Variance (ANOVA) was employed to compare differences in responses between the United Kingdom; Ireland; Portugal; Poland; Norway; the Netherlands; Germany; and, Spain. The results indicated that respondents in Greece, Poland, Ireland, Portugal and Spain, rated the benefits of personalised nutrition highest, suggesting a particular readiness in these countries to adopt personalised nutrition interventions. Greek participants were more likely to perceive the social context of eating as a barrier to adoption of personalised nutrition, implying a need for support in negotiating social situations while on a prescribed diet. Those in Spain, Germany, Portugal and Poland scored highest on perceived barriers related to data protection. Government was more trusted than commerce to deliver and provide information on personalised nutrition overall. This was particularly the case in Ireland, Portugal and Greece, indicating an imperative to build trust, particularly in the ability of commercial service providers to deliver personalised dietary regimes effectively in these countries. These findings, obtained from a nationally representative sample of EU citizens, imply that a parallel, integrated, public-private delivery system would capture the needs of most potential consumers.
Food4me is the acronym of the EU FP7 Project ‘‘Personalised nutrition: an integrated analysis of opportunities and challenges” (Contract No. KBBE.2010.2.3-02, ProjectNo.265494), http:// www.food4me.org/.
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38

Školníková, Elena. "Nutrigenomická analýza vlivu diety v průběhu prenatálního a časného vývoje na manifestaci aspektů metabolického syndromu v dospělosti." Doctoral thesis, 2021. http://www.nusl.cz/ntk/nusl-437899.

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16 Abstract The rising prevalence in noncommunicable diseases worldwide calls for the effort to determine their underlying causes. Common metabolic disorders in particular overwhelm the healthcare systems and are a one of the leading causes of poor quality of life of patients. Metabolic syndrome is represented by concurrence of several conditions - dyslipidaemia, obesity, hypertension or impaired glucose tolerance - altered metabolic phenotypes related to genetic and environmental factors. Recent studies suggest that early-life exposure to certain environmental stimuli is particularly capable of changing the mammalian phenotypes. Nutrition, as one of the major factors influencing health, is naturally a focus of research, which studies the link between parental diets and phenotypic alterations in offspring. The developmental origins of health and disease were historically more focused on maternal undernutrition, it is, however, more important to focus on surplus of macronutrients considering the westernization of modern diets. We propose the relevancy of not only the amount of macronutrients in maternal diet, but also their sources, as they may increase disease risk in offspring. Here we report, that sucrose as an alternative carbohydrate in maternal diet, has a marked impact on metabolism of the offspring...
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39

Brathwaite, Joanne Margaret. "Genetic Variability in Caffeine Acute Effects and Withdrawal Symptoms." Thesis, 2011. http://hdl.handle.net/1807/29497.

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The mechanisms underlying caffeine’s acute effects and withdrawal symptoms are not entirely understood. The purpose was to determine whether the clusters of acute effects or withdrawal symptoms are associated with genetic polymorphisms in DARPP-32 and COMT, which mediate some of caffeine’s physiological effects. Subjects (n=1135) were from the Toronto Nutrigenomics and Healthy Study. Fourteen well-described acute effects of caffeine co-exist in six groups, while fourteen well-characterized withdrawal symptoms co-exist in three groups. Neither the rs907094 C>T polymorphism in the PPP1R1B gene encoding DARPP-32, nor the COMT Val158Met affected the odds of reporting any acute effects or withdrawal symptoms cluster. Among individuals consuming ≥ 200 mg/d of caffeine, Met/Met homozygotes were more likely to report the “increased heart rate” acute effects cluster. These results suggest that ‘slow’ COMT activity, conferred by the Met allele, may explain part of the inter-individual variability in the risk for increased heart rate among heavy caffeine consumers.
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40

Fallaize, R., A. L. Macready, L. T. Butler, J. A. Ellis, A. Berezowska, A. R. H. Fischer, M. C. Walsh, et al. "The perceived impact of the National Health Service on personalised nutrition service delivery among the UK public." 2015. http://hdl.handle.net/10454/7211.

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Yes
Personalised nutrition (PN) has the potential to reduce disease risk and optimise health and performance. Although previous research has shown good acceptance of the concept of PN in the UK, preferences regarding the delivery of a PN service (e.g. online v. face-to-face) are not fully understood. It is anticipated that the presence of a free at point of delivery healthcare system, the National Health Service (NHS), in the UK may have an impact on end-user preferences for deliverances. To determine this, supplementary analysis of qualitative data obtained from focus group discussions on PN service delivery, collected as part of the Food4Me project in the UK and Ireland, was undertaken. Irish data provided comparative analysis of a healthcare system that is not provided free of charge at the point of delivery to the entire population. Analyses were conducted using the ‘framework approach’ described by Rabiee (Focus-group interview and data analysis. Proc Nutr Soc 63, 655-660). There was a preference for services to be led by the government and delivered face-to-face, which was perceived to increase trust and transparency, and add value. Both countries associated paying for nutritional advice with increased commitment and motivation to follow guidelines. Contrary to Ireland, however, and despite the perceived benefit of paying, UK discussants still expected PN services to be delivered free of charge by the NHS. Consideration of this unique challenge of free healthcare that is embedded in the NHS culture will be crucial when introducing PN to the UK.
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41

Nicolaou, Anna, S. M. Pilkington, L. E. Rhodes, and R. B. Watson. "Omega-3 Polyunsaturated Fatty Acids: Photoprotective Macronutrients." 2011. http://hdl.handle.net/10454/5227.

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No
Ultraviolet radiation (UVR) in sunlight has deleterious effects on skin, while behavioural changes have resulted in people gaining more sun exposure. The clinical impact includes a year-on-year increase in skin cancer incidence, and topical sunscreens alone provide an inadequate measure to combat overexposure to UVR. Novel methods of photoprotection are being targeted as additional measures, with growing interest in the potential for systemic photoprotection through naturally sourced nutrients. Omega-3 polyunsaturated fatty acids (n-3 PUFA) are promising candidates, showing potential to protect the skin from UVR injury through a range of mechanisms. In this review, we discuss the biological actions of n-3 PUFA in the context of skin protection from acute and chronic UVR overexposure and describe how emerging new technologies such as nutrigenomics and lipidomics assist our understanding of the contribution of such nutrients to skin health.
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42

Rankin, A., B. P. Bunting, R. Poinhos, der Lans I. A. van, A. R. H. Fischer, L. J. Frewer, and Barbara Stewart-Knox. "Food choice motives, attitudes toward and intention to adopt personalised nutrition." 2018. http://hdl.handle.net/10454/15509.

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yes
Objective: This study explored associations between food choice motives, attitudes towards, 5 and intention to adopt personalised nutrition in order to inform communication strategies 6 based on consumer priorities and concerns. Design and Setting: A survey was administered 7 online which included the food choice questionnaire (FCQ), and items assessing attitudes 8 towards and intention to adopt personalised nutrition. Participants: Nationally representative 9 samples were recruited in 9 EU countries (N=9381). Results: Structural equation modelling 10 indicated that the food choice motives, weight control, mood, health and ethical concern had 11 a positive association and price had a negative association with attitude towards, and 12 intention to adopt, personalised nutrition. Health was positively associated and familiarity 13 negatively associated with attitude toward personalised nutrition. The effects of weight 14 control, ethical concern, mood and price on intention to adopt personalised nutrition were 15 partially mediated by the attitude. The effects of health and familiarity were fully mediated 16 by attitude. Sensory appeal was negatively and directly associated with intention to adopt 17 personalised nutrition. Conclusion: Personalised nutrition providers may benefit from taking 18 into consideration the importance of underlying determinants of food choice, particularly 19 weight control, mood and price, in potential users when promoting services and in tailoring 20 communications that are motivationally relevant.
Post peer-review accepted manuscript; changes are in red.
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43

Day-Tasevski, Erica. "Genetic Determinants of the Acute Effects and Withdrawal Symptoms of Caffeine." Thesis, 2010. http://hdl.handle.net/1807/24245.

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The mechanisms underlying caffeine’s acute effects and withdrawal symptoms are not entirely understood. The purpose was to determine whether these effects or symptoms co-exist in clusters, and whether they are associated with polymorphisms in β1- and β2-adrenoceptors. Subjects (n=1271) were from the Toronto Nutrigenomics and Health Study. The acute effects and withdrawal symptoms clustered into 4 and 6 factors, respectively. Subjects with the ADRβ2 Gly16Arg Gly/Arg genotype were more likely than Gly allele homozygotes to report “fatigue” withdrawal symptoms. Among >200 mg/d caffeine consumers, ADRβ2 Gly allele carriers had a greater risk, compared to Arg allele homozygotes, of reporting ‘flu-like somatic’ withdrawal symptoms. Among subjects with the CYP1A2 -163 A>C A/A genotype and 100-200 mg/d caffeine consumers, ADRβ1 Arg389Gly Gly allele carriers had a greater risk, compared to Arg allele homozygotes, of reporting “dysphoric mood” withdrawal symptoms. The findings suggest that β1- and β2- adrenoceptors play a role in caffeine withdrawal.
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44

Stewart-Knox, Barbara, A. Rankin, S. Kuznesof, R. Poinhos, Almeida M. D. V. de, A. R. H. Fischer, and L. J. Frewer. "Promoting healthy dietary behaviour through personalised nutrition: technology push or technology pull?" 2014. http://hdl.handle.net/10454/6720.

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Yes
The notion of educating the public through generic healthy eating messages has pervaded dietary health promotion efforts over the years and continues to do so through various media, despite little evidence for any enduring impact upon eating behaviour. There is growing evidence, however, that tailored interventions such as those that could be delivered online can be effective in bringing about healthy dietary behaviour change. The present paper brings together evidence from qualitative and quantitative studies that have considered the public perspective of genomics, nutrigenomics and personalised nutrition, including those conducted as part of the EU-funded Food4Me project. Such studies have consistently indicated that although the public hold positive views about nutrigenomics and personalised nutrition, they have reservations about the service providers’ ability to ensure the secure handling of health data. Technological innovation has driven the concept of personalised nutrition forward and now a further technological leap is required to ensure the privacy of online service delivery systems and to protect data gathered in the process of designing personalised nutrition therapies.
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45

Rankin, A., B. P. Bunting, R. Poinhos, der Lans I. A. van, A. R. H. Fischer, S. Kuznesof, M. D. V. Almeida, Jerko Markovina, L. J. Frewer, and Barbara Stewart-Knox. "Food choice motives, attitude towards and intention to adopt personalised nutrition." 2018. http://hdl.handle.net/10454/18166.

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Yes
The present study explored associations between food choice motives, attitudes towards and intention to adopt personalised nutrition, to inform communication strategies based on consumer priorities and concerns. Design/Setting: A survey was administered online which included the Food Choice Questionnaire (FCQ) and items assessing attitudes towards and intention to adopt personalised nutrition. Subjects: Nationally representative samples were recruited in nine EU countries (n 9381). Results: Structural equation modelling indicated that the food choice motives ‘weight control’, ‘mood’, ‘health’ and ‘ethical concern’ had a positive association and ‘price’ had a negative association with attitude towards, and intention to adopt, personalised nutrition. ‘Health’ was positively associated and ‘familiarity’ negatively associated with attitude towards personalised nutrition. The effects of ‘weight control’, ‘ethical concern’, ‘mood’ and ‘price’ on intention to adopt personalised nutrition were partially mediated by attitude. The effects of ‘health’ and ‘familiarity’ were fully mediated by attitude. ‘Sensory appeal’ was negatively and directly associated with intention to adopt personalised nutrition. Conclusions: Personalised nutrition providers may benefit from taking into consideration the importance of underlying determinants of food choice in potential users, particularly weight control, mood and price, when promoting services and in tailoring communications that are motivationally relevant.
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46

Μπαράκου, Αγλαΐα. "Υπηρεσίες διατροφογονιδιωματικής : απήχηση και κατανόηση του ρόλου τους από το ελληνικό κοινό." Thesis, 2012. http://hdl.handle.net/10889/5454.

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Η παρούσα εργασία αποτελεί μια πρώτη προσπάθεια αξιολόγησης της απήχησης των υπηρεσιών Διατροφογονιδιωματικής στην Ελλάδα, που ακόμα είναι ελάχιστα αναπτυγμένες στην χώρα μας. Στόχος της είναι η κατανόηση των στάσεων και απόψεων του ελληνικού κοινού αναφορικά με τη σχέση γενετικής και διατροφής. Με τη μελέτη αυτή επιδιώκουμε επίσης να εκτιμήσουμε το επίπεδο γνώσεων και το ενδιαφέρον του ευρέος κοινού στους τομείς αυτούς και να σκιαγραφήσουμε τη διάθεσή τους να υποβληθούν σε γενετικές εξετάσεις με στόχο την συσχέτιση του γενετικού τους προφίλ με τη διατροφή τους και την ακόλουθη λήψη διαιτητικών συστάσεων. Για τους σκοπούς της έρευνας συντάχθηκε ένα Ερωτηματολόγιο με 16 ερωτήσεις κλειστού τύπου. Το δείγμα μας αποτέλεσαν 300 τυχαία επιλεγμένα άτομα στην πόλη της Πάτρας, που δέχτηκαν να απαντήσουν στο Ερωτηματολόγιο. Οι απαντήσεις μελετήθηκαν σε σχέση με το Φύλο, την Ηλικιακή Ομάδα και τον Δείκτη Σωματικού Βάρους των ερωτηθέντων, για να ελεγχθεί πιθανή επίδραση των παραγόντων αυτών στις απαντήσεις τους. Τα αποτελέσματά μας καταγράφουν ότι το ευρύ κοινό στην Ελλάδα εμφανίζεται να γνωρίζει τι είναι DNA και γενετικό υλικό καθώς και το ρόλο των γονιδίων στον καθορισμό της υγείας. Επίσης, φαίνεται να υπάρχει μια καλή θεώρηση της σχέσης μεταξύ διατροφής και υγείας. Υψηλό ποσοστό του κοινού εμφανίζονται ενήμεροι σχετικά με τα πιθανά οφέλη των γενετικών αναλύσεων, αν και το ποσοστό αυτό μειώνεται με την ηλικία. Τα δεδομένα μας έδειξαν ότι μόνο στο 9.7% από τους ερωτηθέντες έχει προταθεί να υποβληθούν σε μια γενετική εξέταση για τη σχέση γονιδίων και διατροφής, παρόλο που το 84% των συμμετεχόντων απάντησαν ότι θα ήταν διατεθειμένοι να το κάνουν. Ενδιαφέρον επίσης παρουσιάζει το γεγονός ότι η μεγάλη πλειοψηφία του κοινού προτιμά την παραπομπή ενός γιατρού για μια τέτοια εξέταση και πολύ λιγότερο τη συμβουλή ενός διατροφολόγου/διαιτολόγου. Συμπερασματικά, η μελέτη αυτή αποτελεί την πρώτη κριτική αξιολόγηση των απόψεων του ευρέος κοινού στην Ελλάδα όσον αφορά στις υπηρεσίες γενετικών εξετάσεων με στόχο συμβουλευτική διατροφής. Εφόσον δεν έχει διεξαχθεί άλλη τέτοια έρευνα, θεωρούμε ότι θα μπορούσε να χρησιμεύσει σαν πρότυπο για να μελετηθούν και άλλοι πληθυσμοί, και να στοχευθούν καλύτερα εκείνοι που: α) έχουν πραγματική ανάγκη τέτοιων αναλύσεων (πχ οικογενειακό ιστορικό παχυσαρκίας η καρδιαγγειακών νοσημάτων) και β) είναι επιστημονικά στοιχειωδώς ενήμεροι και φαίνονται διατεθειμένοι να υποβληθούν στις ανάλογες αναλύσεις (άρα έχουν εμπιστοσύνη στην αποτελεσματικότητά τους).
This research constitutes a first attempt to understand the general public’s knowledge concerning basic notions and services in genetics-based nutrition, as well as reveal their attitudes and perceptions on Nutrigenomics. With this research we also aspire to assess the level of knowledge an interest of the general public in this field and evaluate their willingness to undergo such genetic analyses, in order to correlate their genetic profile with their nutrition and receive dietary recommendations. For the purposes of this study, we designed a questionnaire of 16 questions and conducted a general public survey. Our sample consists of 300 participants, randomly chosen from the public, in the city of Patras in Greece. The answers were analyzed by grouping them according to Gender, Age group and the BMI of the participants, in order to check for potential influence of these factors on the answers. Our analysis indicated that the public in Patras appears quite knowledgeable concerning DNA and the role of the genome in determining overall health. Participants also have a good grasp of the relation of nutrition to health conditions. A large proportion of the general public is aware of the existence of gene-based disorders and the potential benefits of genetic testing, although this proportion declines steadily with age. Our data revealed that only 9.7% of respondents from the general public had been advised to take a genetic test in order to explore the relationship between their genes and their nutritional status. However, 84% of them would be willing to undergo nutrigenomic analysis to correlate their genetic profile with their diet. Interestingly, to do so, the vast majority of the general public would prefer referral from a physician than from a dietitian/nutritionist. Our study has provided the first critical evaluation of the views of the general public with regard to genetics and genetic testing services in Greece and, since no other such study has been conducted so far, it should serve as a model for replication in other populations, so that we could target the groups that a) are in need of such analyses due to family history of obesity or cardiovascular disease, and b) are fundamentally scientifically aware and seem willing to undergo such tests.
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47

Knoch, Bianca. "The effects of dietary eicosapentaenoic acid and arachidonic acid on gene expression changes in a mouse model of human inflammatory bowel diseases : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Nutritional Science at Massey University, Palmerston North, New Zealand." 2010. http://hdl.handle.net/10179/1529.

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Nutrigenomics studies the genome-wide influence of nutrients to understand the association between nutrition and human health. Studies in animal models and humans have demonstrated that dietary n-3 polyunsaturated fatty acids (PUFA) from fish oil may be beneficial in inflammatory bowel diseases (IBD). This thesis aimed to test the hypothesis that dietary n-3 PUFA eicosapentaenoic acid (EPA) reduced and n-6 PUFA arachidonic acid (AA) increased colitis in the interleukin- 10 gene-deficient (Il10–/–) mouse model of IBD, and that these PUFA altered the intestinal bacteria community during colitis development using genome-wide expression and bacterial profiling. Using a combined transcriptomic and proteomic approach, the time-course study defined the onset and progression of colitis in Il10–/– mice. Histopathology, transcript and protein changes before and after colitis onset involved in innate and adaptive immune responses suggested delayed remodelling processes in colitic Il10–/– mice and 11 weeks of age as suitable time point to study the effects of dietary PUFA on colitis development. Comparing the transcriptome and proteome profiles associated with colon inflammation of mice fed with the AIN-76A or oleic acid (OA) diet showed that OA was an appropriate control for unsaturated fatty acids in multi-omic studies. The PUFA intervention study indicated that dietary EPA-induced lipid oxidation might have a potential anti-inflammatory effect on inflamed colon tissue partially mediated through activation of peroxisome proliferator-activated receptor alpha (PPARα). Unexpectedly, dietary AA decreased the expression of inflammatory and stress colonic genes in Il10–/– mice. Altered intestinal bacteria community observed in Il10–/– mice before and after colitis onset was associated with the lack of IL10 protein led to changes in intestinal metabolic and signalling processes. Interestingly, dietary EPA and AA seemed to change intestinal bacteria profiles during colitis development. The role of PPARα in the colon was further examined in a concluding study which identified vanin1 as a likely new PPARα-target gene which may also be involved in lipid metabolism. These findings using a state-of-the-art approach combining transcriptomics, proteomics and physiology provide a basis for future research on molecular mechanisms underlying the effects of dietary PUFA, and might contribute to the development of fortified foods that improve intestinal health and wellness.
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48

Cahill, Leah Elizabeth. "Genetic Determinants of Serum Ascorbic Acid Concentrations." Thesis, 2010. http://hdl.handle.net/1807/26134.

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Background: The adequacy of serum ascorbic acid (vitamin C) concentrations in young Canadian adults is unknown. Individuals have varied serum ascorbic acid response to dietary vitamin C, possibly due to genetic variation. Objective: To investigate the prevalence of serum ascorbic acid deficiency in young Canadians and to determine whether common genotypes modify the association between dietary vitamin C and serum ascorbic acid. Methods: Subjects were 1277 men and women aged 20-29 years from the Toronto Nutrigenomics and Health study. Vitamin C intakes were estimated by a 196-item FFQ. Fasting blood was collected to measure serum ascorbic acid by HPLC and to genotype for common polymorphisms in genes that code for glutathione S-transferase (GST) (GSTM1, GSTT1 and GSTP1), haptoglobin (Hp), and vitamin C transporters (SLC23A1 and SLC23A2). Results: 53% of subjects had adequate, 33% had suboptimal and 14% had deficient serum ascorbic acid. Subjects with deficiency had higher mean C-reactive protein, waist circumference, BMI and blood pressure than subjects with adequate serum ascorbic acid. The odds ratio (95% confidence interval) for serum ascorbic acid deficiency was 3.43 (2.14, 5.50) for subjects who did not meet the vitamin C recommendation compared to those who did. The corresponding odds ratios were 2.17 (1.10, 4.28) and 12.28 (4.26, 33.42) for individuals with the GSTT1 functional and null genotypes respectively (interaction p=0.01), and 2.29 (0.96, 5.45) and 4.03 (2.01, 8.09) for the GSTM1 functional and null genotypes (interaction p=0.04). These odds ratios were 4.77 (2.36, 9.65) for the Hp2-2 genotype, but 1.69 (0.80, 3.63) for carriers of the Hp1 allele (interaction p=0.02). Serum ascorbic acid concentrations (mean +/- SE) differed among SLC23A1 rs4257763 genotypes (GG: 24.4 +/- 1.3, GA: 26.8 +/- 1.1, AA: 29.7 +/- 1.4, p=0.002). Conclusions: Serum ascorbic acid deficiency is prevalent and associated with markers of chronic disease. Individuals with GST null or Hp2-2 genotypes had an increased risk of deficiency if they did not meet the recommendation for vitamin C, suggesting that GSTs and haptoglobin may spare ascorbic acid when dietary vitamin C is insufficient, thus protecting against serum ascorbic acid deficiency.
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49

Garofalo, Francesca. "Genetic Determinants of Plasma alpha-tocopherol." Thesis, 2012. http://hdl.handle.net/1807/35516.

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alpha-tocopherol is the most abundant form of vitamin E in human plasma and tissues. Inter-individual differences in plasma alpha-tocopherol concentration or its response to dietary alpha-tocopherol may be due, in part, to polymorphisms in vitamin E metabolism genes (alpha-tocopherol transfer protein (alpha-TTP), tocopherol associated protein (TAP) and CYP4F2). The thesis objectives were to determine whether common polymorphisms in the alpha-TTP (rs6994076 A>T), TAP (rs2072157 C>T and Arg11Lys) and CYP4F2 (Val433Met) genes influence plasma alpha-tocopherol concentration or modify the association between dietary and plasma alpha-tocopherol. Subjects (n=1248), 20 to 29 years from the Toronto Nutrigenomics and Health study completed a food frequency questionnaire. Fasting blood samples were used for genotyping and to measure plasma alpha-tocopherol concentration. The alpha-TTP and TAP Arg11Lys polymorphisms significantly altered plasma alpha-tocopherol. The alpha-TTP polymorphism only influenced plasma alpha-tocopherol in individuals not using supplements. None of the polymorphisms examined modified the plasma alpha-tocopherol response to dietary alpha-tocopherol.
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50

Stewart-Knox, Barbara, B. P. Bunting, S. Gilpin, H. J. Parr, S. Pinhao, J. J. Strain, Almeida M. D. V. de, and M. J. Gibney. "Attitudes toward genetic testing and personalised nutrition in a representative sample of European consumers." 2009. http://hdl.handle.net/10454/6206.

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Negative consumer opinion poses a potential barrier to the application of nutrigenomic intervention. The present study has aimed to determine attitudes toward genetic testing and personalised nutrition among the European public. An omnibus opinion survey of a representative sample aged 14-55+ years (n 5967) took place in France, Italy, Great Britain, Portugal, Poland and Germany during June 2005 as part of the Lipgene project. A majority of respondents (66 %) reported that they would be willing to undergo genetic testing and 27 % to follow a personalised diet. Individuals who indicated a willingness to have a genetic test for the personalising of their diets were more likely to report a history of high blood cholesterol levels, central obesity and/or high levels of stress than those who would have a test only for general interest. Those who indicated that they would not have a genetic test were more likely to be male and less likely to report having central obesity. Individuals with a history of high blood cholesterol were less likely than those who did not to worry if intervention foods contained GM ingredients. Individuals who were aware that they had health problems associated with the metabolic syndrome appeared particularly favourable toward nutrigenomic intervention. These findings are encouraging for the future application of personalised nutrition provided that policies are put in place to address public concern about how genetic information is used and held.
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