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1
Groeneveld, Matthijs Pieter. „In vitro modelling of proximal insulin signalling defects in adipocytes : insights into monogenic human disorders“. Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648407.
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2
McLane, Jesica Mata. „Investigation of 1alpha,25-dihydroxy vitamin D3 membrane receptor ERp60 in adipocytes from male and female lean and obese mice“. Thesis, Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/31793.
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Thesis (M. S.)--Biomedical Engineering, Georgia Institute of Technology, 2010.Committee Chair: Dr. Barbara Boyan; Committee Co-Chair: Dr. Zvi Schwartz; Committee Member: Dr. Hanjoong Jo. Part of the SMARTech Electronic Thesis and Dissertation Collection.
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Farré, Guasch Elisabet. „Adipose Stem Cells from Buccal Fat Pad and Abdominal Adipose Tissue for Bone tissue Engineering“. Doctoral thesis, Universitat Internacional de Catalunya, 2011. http://hdl.handle.net/10803/31987.
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ABSTRACT
Background and Objective: Stem cells offer an interesting tool for tissue engineering, but the clinical applications are limited by donor site morbidity and low cell number upon harvest. Recent studies have identified an abundant source of stem cells in subcutaneous adipose tissue. These adipose stem cells (ASC), are able to differentiate to several lineages and express multiple growth factors, which makes them suitable for clinical application. Buccal fat pad (BFP), an adipose encapsulated mass in the oral cavity, could represent an easy access source for dentists and oral surgeons. Biosynthetic substitutes such as β-tricalcium phosphate (β-TCP), hydroxyapatite (HA), and mixtures of HA/β-TCP (biphasic calcium phosphate; BCP) have been successfully used as bone graft biomaterials. Growth factors stimulating osteogenic differentiation are also interesting for bone tissue engineering applications. We aimed to investigate whether BFP is a rich source of ASC, and whether ASC triggered for only 15 min with bone morphogenetic protein-2 (BMP-2), and seeded onto different calcium phosphate scaffolds composed of β-TCP alone or mixtures of HA/β-TCP, could stimulate bone formation.
Materials & Methods: ASC obtained from subcutaneous abdominal adipose tissue and BFP were counted and analyzed by flow cytometry, to determine ASC cell number, phenotype and percentage. At two weeks of culture, the multipotent differentiation potential of ASC from BFP was analyzed. Furthermore, fresh ASC either or not stimulated with 10ng/ml BMP-2 for 15min were seeded on different calcium phosphate scaffolds. ASC attachment, proliferation and osteogenic differentiation was analyzed and compared.
Results: BFP contained ~30% of ASC. The ASC number obtained per gram of adipose tissue from BFP at one week of culture was 2-fold higher than in subcutaneous abdominal adipose tissue. Angiogenic marker expression was also higher, and ASC showed multipotent differentiation potential as well. Fifteen min BMP-2 treatment increased ASC cell proliferation and osteogenic differentiation on BCP composed of 60% HA and 40% β-TCP, but not on other scaffolds containing less percentage of HA.
Conclusions: Buccal fat pad is a rich alternative source of ASC suitable for bone tissue engineering. Short stimulation of only 15 minutes with BMP-2 is enough to stimulate ASC proliferation and osteogenic differentiation. Therefore ASC could be treated shortly with BMP-2 and seeded on BCP with 60% HA to improve bone regeneration.
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Foster, Michelle Tranace. „Central nervous system regulation of fat cell lipid mobilization the role of the sympathetic nervous system /“. restricted, 2005. http://etd.gsu.edu/theses/available/etd-11162005-154631/.
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Thesis (Ph. D.)--Georgia State University, 2005.Timothy Bartness, committee chair; Elliott Albers, Ruth Harris , Sarah Pallas, committee members. Electronic text (181 p. : ill.)) : digital, PDF file. Description based on contents viewed July 17, 2007. Includes bibliographical references (p. 148-181).
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Lee, Pui-chi, und 李佩芝. „Phenotypic characterization of adipocyte fatty acid binding protein knockout mice under high fat high cholesterol diet-induced obesity“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/197517.
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Background and objectives:
A lot of studies proved that adipocyte fatty acid binding protein (A-FABP), an adipokine mainly expressed in adipocytes and macrophages, is the key link between obesity and inflammation which is suggested to be a therapeutic target for obesity-related diseases. Loss-of-function study was employed by using A-FABP knockout (KO) mice generated by our group to investigate role of A-FABP in high fat high cholesterol (HFHC) diet-induced obesity.
Key findings:
1. Our study confirmed that HFHC diet-induced A-FABP KO mice have a significantly increased body weight when compared to the wild-type (WT) control mice.
2. Higher adiposity was the major reason for the A-FABP KO mice to be heavier than the WT controls under HFHC diet induction.
3. The marked increase of the weight of subcutaneous fat and peri-renal fat contributed to the higher adiposity of the HFHC-diet induced A-FABP KO mice when compared to the WT controls.
4. The HFHC-diet induced A-FABP KO mice significantly consumed less oxygen and produced less carbon dioxide suggesting the reduced energy expenditure but had higher weekly energy intake when compared with the WT controls, leading to higher adiposity.
5. The A-FABP KO mice were protected against HFHC diet induced glucose intolerance, insulin resistance, hyperglycemia and hyperinsulinemia when compared with the WT controls. There was also a better insulin secretion in response to glucose stimulation in A-FABP KO mice under prolonged HFHC diet induction when compared with the WT controls.
6. The A-FABP KO mice were protected against the development of hypercholesterolemia and hypertriglycemia when compared the WT controls under HFHC diet induction. However, there was no significant difference in the fasting serum free fatty acids (FFA) level among A-FABP WT and KO mice fed with standard chow (STC) or HFHC diet.
7. A-FABP KO mice were protected against isolated systolic hypertension (ISH) under HFHC diet induction.
8. The A-FABP KO mice were protected against HFHC diet-induced liver injury as indicated by a lower serum ALT level suggesting a better liver function when compared with the WT controls.
9. Under HFHC diet induction, M1 macrophage polarization was dominant in fat tissues of A-FABP WT mice but M2 macrophage polarization was dominant in fat tissues of A-FABP KO mice, suggesting an improved inflammatory status in the adipose tissue of the A-FABP KO mice when compared with the WT controls. This may also be the reason for why HFHC diet-induced A-FABP KO mice have an increased body weight but are metabolically healthier compared to their WT controls.
Conclusions:
A-FABP KO mice had a significant higher body weight and higher adiposity due to the reduced energy expenditure and increased weekly food intake as indicated in the metabolic cage study and the reason for metabolic healthier is due to the alleviated HFHC diet induced M1 macrophage polarization in various adipose tissues suggesting an improved inflammatory status in A-FABP KO mice comparing to the WT controls.published_or_final_version
Medicine
Master
Master of Philosophy
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Skolnick, Sara A. „Hormone-stimulated lipolysis in the aging rat“. Virtual Press, 1989. http://liblink.bsu.edu/uhtbin/catkey/562784.
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The normal development of adipose tissue lipolysis as measured by glycerol release was studied in epididymal fat pads of Sprague-Dawley rats between 4 and 16 weeks of age and correlated with changes in fat cell size.For each age group studied, 4 weeks, 8 weeks, and 16 weeks of age, basal (no hormone present) and hormone stimulated lipolytic activity were observed for two concentrations of epinephrine were used, maximal (10,00 nM) and minimal (10 nM). Basal levels of glycerol were not linear. There was an increase between 4 and 8 weeks of age followed by a decrease between 8 and 16 weeks of age. The maximal dosage of hormone evoked a large increase in 9lYcerol production between 4 and 8 weeks, which was followed by a decrease between 8 and 16 weeks of age. The minimal dosage of epinephrine, although not significant, showed a decrease in glycerol production from 4 to 16 weeks of age. Fat cell size continued to increase between 4 and 16 weeks. Both fat cell diameter and volumes underwent a linear increase with age. However, the change was not reflected in epinephrine stimulated glycerol release. Therefore, glycerol release is inversely correlated with fat cell size during early development.The results indicate that age influences hormone stimulated lipolysis and is not dependent on cell size. Although the mechanism for the decreased lipolytic response of the isolated adipocytes was not discovered, it is believed that it may be due in part to a reduced number of receptors and to a reduced sensitivity of the cellular enzymatic system underlying lipolysis.School of Physical Education
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So, Wing-yan. „Proteome and gene expression analysis in white adipose tissue of diet-induced obese mice“. Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B39367435.
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Randhawa, Manpreet Kaur. „An ectopic synthesis of the melanin in the adipocytes of the morbidly obese subjects“. Fairfax, VA : George Mason University, 2008. http://hdl.handle.net/1920/3231.
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Thesis (Ph.D.)--George Mason University, 2008.Vita: p. 221. Thesis director: Ancha Baranova. Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biosciences. Title from PDF t.p. (viewed Aug. 28, 2008). Includes bibliographical references (p. 168-220). Also issued in print.
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So, Wing-yan, und 蘇詠欣. „Proteome and gene expression analysis in white adipose tissue of diet-induced obese mice“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39367435.
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Bellenzani, Marcela Palomo Pieroni 1984. „Expressão de enzimas envolvidas na produção de triacilglicerol em tecidos adiposo e hepático isolados de ratos normo e hiperlipidêmicos“. [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314094.
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Orientador: Dora Maria Grassi KassisseDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-20T14:23:50Z (GMT). No. of bitstreams: 1 Bellenzani_MarcelaPalomoPieroni_M.pdf: 6472856 bytes, checksum: e473a96a17b23ee1d9a456d9ac7a4602 (MD5) Previous issue date: 2012
Resumo: A pandemia da obesidade é evidente no início do século XXI. O fator desencadeante mais relevante é a alimentação hipercalórica associada ao sedentarismo. Modelos de estudo em ratos para investigar as etapas que precedem o desenvolvimento desta doença são fundamentais para propor terapias de prevenção. No modelo de indução da dislipidemia pela dieta por quatro semanas, os ratos apresentam hipercolesterolemia, hipertrigliceridemia e hiperinsulinemia e com seis semanas de administração da dieta observa-se um aumento no peso dos panículos adiposos da região epididimal e peri-renal e sem alteração no depósito da região mesentérica. Assim sendo, objetivamos, nesta tese, analisar as vias metabólicas envolvidas no processo de metabolização da glicose e triacilgliceróis nos tecidos adiposo branco e hepático em ratos hiperlipidêmicos e para tal estudamos as vias lipogênica, lipolítica e neoglicogênica, pela quantificação da expressão gênica das enzimas chaves envolvidas nestes processos. A dislipidemia foi induzida pelo oferecimento de dieta hiperlipídica (grupo dieta, D) ao longo de quatro semanas a ratos jovens e a instalação do quadro foi verificada pelas análises plasmáticas ao final do tratamento e após jejum de 16h. Amostras de tecidos hepático e adiposo foram coletadas para análise histológica e quantificação da expressão gênica sendo estas analisadas por qRT-PCR. Observou-se que ratos que ingerem dieta hiperlipídica (+129+10,13 g) ganham peso de forma semelhante aos ratos controle (C: +148+8,8 g) mesmo ingerindo quantidade significativamente menor de dieta (C: 20,8+0,62 g vs D: 14,87+0,66 g). As análises histológicas ilustram aumento no teor de depósitos de lipídeos no tecido hepático. A expressão gênica no tecido hepático de ratos dieta foi aumentada significativamente para as enzimas lipoproteína lipase, piruvato desidrogenase quinase 4 e fosfofrutoquinase 1 e diminuição significativa na expressão de glicose 6-fosfatase sem alteração na quantificação da expressão de acetil-CoA carboxilase alpha, gliceroquinase, piruvato desidrogenase fosfatase 2. Em relação ao tecido adiposo observamos que a expressão das enzimas acetil-CoA carboxilase e piruvato desidrogenase fosfatase 2 não foi significativamente alterada em nenhum dos depósitos adiposos. A lipase hormônio-sensível não apresentou alterações no tecido adiposo epididimal, porém teve sua expressão significativamente aumentada nos tecidos mesentérico e peri-renal. A expressão da lipoproteína lipase por sua vez, não se alterou no panículo adiposo epididimal nem no panículo adiposo mesentérico estando diminuída no panículo adiposo peri-renal. E por fim, a piruvato desidrogenase quinase 4 também não apresentou alterações nos depósitos epididimal e mesentérico porém no peri-renal sua expressão encontrou-se aumentada. Estes resultados, em conjunto, indicam que a dieta administrada por 4 semanas, mesmo não apresentando todas as alterações observadas com 6 semanas, pode ser útil para os estudos iniciais do quadro de dislipidemia que antecedem as disfunções metabólicas
Abstract: The pandemic of obesity is evident in the twenty-first century. The most important and triggering factor is the high-calorie diet associated with physical inactivity. Study models in rats to investigate the steps that precede the development of this disease are essential to propose preventive therapies. In the model of induction of dyslipidemia by diet for four weeks, the mice exhibit hypercholesterolemia, hypertriglyceridemia, and hyperinsulinemia and there is an increase in weight of the panniculus region of epididymal and peri-renal depot and no change in the mesenteric region. Therefore, we aimed to analyze the metabolic pathways involved in the metabolism of glucose and triglycerides in white adipose tissue, and liver in hyperlipidemic rats and to study the ways that lipogenic, lipolytic and glyconeogenic for the quantification of gene expression of key enzymes involved in these processes. Dyslipidemia was induced by offering high-fat diet (diet group, D) over four weeks to young rats and onset of condition was verified by analysis at the end of the plasma treatment and after fasting for 16 hours. Samples of liver and adipose tissue were collected for histological analysis and quantification of gene expression and these were analyzed by qRT-PCR. It was observed that mice eat high-fat diet (+129 +10.13 g) gain weight similarly to control rats (C: +8.8 +148 g) even eating significantly less diet (C: 20.8 +0.62 g vs D: 14.87 +0.66 g). Histological analysis illustrate the content of lipid deposits in liver tissue. Gene expression in liver tissue of rats diet was significantly increased for the enzymes lipoprotein lipase, pyruvate dehydrogenase kinase 4 and 1 and Phosphofructokinase significant decrease in the expression of glucose 6-phosphatase no change in the quantification of the expression of acetyl-CoA carboxylase alpha, Gliceroquinase, pyruvate dehydrogenase phosphatase 2. In relation to the adipose tissue we observed that the expression of the enzyme acetyl-CoA carboxylase and pyruvate dehydrogenase phosphatase 2 was not significantly altered in any of the fatty deposits. The hormone-sensitive lipase showed no changes in epididymal adipose tissue but its expression was significantly increased in mesenteric tissue and peri-renal. Lipoprotein lipase, in turn, did not change in the mesenteric or epididymal being reduced in the peri-renal. And finally, the pyruvate dehydrogenase kinase 4 also showed no changes in epididymal and mesenteric but the peri-renal expression is increased. These results, together, indicate that the diet for 4 weeks, even not showing all changes observed within 6 weeks, can be useful for the initial studies of hyperlipidemia that precede the metabolic dysfunctions
Mestrado
Fisiologia
Mestre em Biologia Funcional e Molecular
11
Negri, Irene. „P2Y2 nucleotide receptor is a regulator of cardiac adipose tissue and its fat-associated lymphoid clusters at basal state and after myocardial infarction“. Doctoral thesis, Universite Libre de Bruxelles, 2020. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/312212.
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The research of new therapeutic strategies for cardiovascular diseases has seen in the last 15 years the introduction of a new participant: pericardial adipose tissue (PAT). This tissue is able to modulate cardiac function and its volume was sometimes linked to risk of cardiovascular diseases. Moreover, adipose-derived stem cells (ASCs) isolated from PAT are considered as the best suitable for new regenerative strategies aiming at healing ischemic myocardium. Although the interests in understanding the functions and the formation of pericardial adipose tissue are high, the current knowledge on this tissue is still scarce. In this work, the starting point was the consideration that nucleotide receptors are established regulators of many biological functions, including the differentiation of adult mesenchymal stem cells, immunity and inflammatory process. The P2Y4 receptor has been recently recognized as a negative regulator of cardiac fat formation and ASCs differentiation. The purpose of this thesis was to analyze the involvement of the nucleotide receptor P2Y2 in the formation of pericardial adipose tissue (PAT) and its ASCs differentiation. We also investigated the possible contribution of this receptor to the functions of recently discovered fat-associated lymphoid clusters (FALCs). Our study analyzed the PAT of mice deficient for P2Y2 at basal conditions and in a model of myocardial infarction. P2Y2-null mice showed a lower mass of PAT compared to WT, which was correlated with decreased adipogenic differentiation and maturation potential of pericardial ASCs in vitro. PAT of basal P2Y2-deficient mice displayed a reduced density of FALCs due to a reduced number of B cells. RNA-sequencing experiments identified many P2Y2 target genes in PAT linked to immunomodulation. We identified a polarization of FALCs macrophages towards anti-inflammatory M2c subtype in P2Y2-null mice. We correlated it with a decreased number of follicular helper T cells, known to contribute to B cell expansion in germinal centers. These data could be correlated with increased apoptosis of B lymphocytes. The data obtained using the mouse infarct model confirmed an expected enlargement of pericardial FALCs in ischemic conditions. P2Y2-null mice were characterized by a reduced expansion of B cells and myeloid cells migration in PAT. These results suggested a participation of P2Y2 receptor in regulating the post-MI inflammatory response by modulating the leukocytes populations in the pericardial adipose tissue’s lymphoid clusters. The effect of P2Y2 on PAT post-ischemic inflammatory state could contribute to the P2Y2-mediated cardioprotective effect of UTP described in previous literature. Our study defines P2Y2 nucleotide receptor as a regulator of the formation of pericardial fat and its inflammatory status in ischemic conditions. P2Y2 receptor could represent an interesting therapeutic target for the regulation of PAT functions before and after MI. In general, a better comprehension of PAT and its consideration in the post-ischemic regeneration process could lead to the development of new therapeutic strategies for treating cardiovascular diseases and the adjustment of existing therapies.Durant les 15 dernières années, un nouvel arrivant a fait son apparition dans la recherche de nouvelles approches thérapeutiques dans le domaine cardiovasculaire: le tissu adipeux cardiaque. Ce tissu est capable de moduler les fonctions cardiaques et son volume a pu être associé parfois à un risque de maladie cardiovasculaire. De plus, les cellules souches dérivées du tissu adipeux (ASCs) cardiaque sont considérées comme les mieux appropriées pour des stratégies thérapeutiques visant la réparation du myocarde ischémié. Bien que la compréhension de la fonction et de la formation du tissu adipeux cardiaque présente un intérêt majeur, la connaissance actuelle de ce tissu particulier est encore assez limitée. Pour le présent travail, le point de départ a été l’observation que les récepteurs nucléotidiques sont des régulateurs établis de nombreuses fonctions biologiques, incluant la différentiation des cellules souches mésenchymateuses et plus généralement la régulation de la réponse immune et inflammatoire. Le récepteur P2Y4 a été récemment reconnu comme un régulateur négatif de la formation du tissu adipeux cardiaque et de la différentiation des ASCs. Le but de cette thèse a été l’étude de l’implication du récepteur nucléotidiques P2Y2 dans la formation du tissu adipeux péricardique (TAP) et la différentiation des ASCs. Nous avons également investigué la contribution possible de ce récepteur dans la fonction des structures leucocytaires associées au tissu adipeux appelées FALCS pour fat-associated lymphoid clusters.Nous avons étudié le TAP de souris déficientes pour le récepteur P2Y2 à l’état de base et dans un modèle d’infarctus du myocarde. Les souris P2Y2 knock-out (KO) présentent une masse réduite du TAP corrélée avec le fait que l’absence du P2Y2 diminue la différentiation adipogénique et le potentiel de maturation des ASCs péricardiques in vitro. Le PAT des souris P2Y2 KO présentent une diminution de la densité de FALCs à l’état de base, principalement due à un nombre réduit de lymphocytes B, potentiellement corrélé à une apoptose accrue observée dans ces cellules. Nos expériences de RNA-sequencing ont identifié de nombreux gènes cibles du P2Y2 dans le PAT impliqués dans l’immunomodulation. Nous avons identifié une polarisation des macrophages de type M2c dans les FALCs de souris P2Y2 KO. Nous l’avons corrélée avec une diminution des lymphocytes T helper folliculaires connus pour contribuer à l’expansion des lymphocytes B dans les centres germinaux. Les données obtenues dans le modèle d’infarctus chez la souris ont confirmé une augmentation des FALCs péricardiques dans les conditions d’ischémie cardiaque. Les souris P2Y2 KO sont caractérisées par une expansion réduite des lymphocytes B et des cellules myéloïdes dans le TAP. Ces résultats suggèrent une participation du récepteur P2Y2 dans la régulation de la réponse inflammatoire post-infarctus par la modulation des populations leucocytaires dans les clusters lymphocytaires du tissu adipeux cardiaque. L’effet du P2Y2 sur l’état inflammatoire post-ischémique pourrait contribuer à l’effet cardioprotecteur de l’UTP médié par le P2Y2 et précédemment décrit dans la littérature.Notre étude définit le récepteur nucléotidique P2Y2 comme un régulateur de la formation du tissu adipeux péricardique et de son niveau inflammatoire dans des conditions ischémiques. Le récepteur P2Y2 pourrait représenter une cible thérapeutique intéressante pour la régulation des fonctions du PAT avant et après infarctus du myocarde. Plus généralement, une meilleure compréhension du tissu adipeux cardiaque et de son implication dans le processus de régénération cardiaque pourrait mener au développement de nouvelles stratégies thérapeutiques dans le traitement de maladies cardiovasculaires et à l’ajustement de thérapies déjà existantes.
Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)
info:eu-repo/semantics/nonPublished
12
Umali, Samantha. „Role of Tyk2 in the Development of Beige Cells“. VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/241.
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Obesity results from an excess of adipose tissue and is a major risk factor for type 2 diabetes, cardiovascular disease, and cancer. Adipose tissue exists in two main forms: white adipose tissue (WAT), which stores energy as triglycerides, and brown adipose tissue (BAT), which dissipates stored energy as heat. White adipose tissue is composed of several subcutaneous and visceral depots, each possessing distinct molecular and functional characteristics. Brown-like adipocytes can emerge in WAT depots in response to cold or beta-adrenergic stimulation. These cells have been called “beige” or “brite” (brown-in-white) cells. The reduction of obesity in mice treated with beta-adrenergic agonists is correlated with the emergence of beige cells. Beige cell development occurs most readily in subcutaneous depots, and to the least extent in visceral depots. Understanding the molecular mechanisms underlying beige cell development in different WAT depots may be important in discovering new therapies against obesity and related diseases. Our lab has previously discovered that Tyrosine Kinase 2 (Tyk2), an important mediator of cytokine signaling, promotes the development of classical brown adipose tissue. Due to the lack of functional BAT, Tyk2-knockout (Tyk2-/-) mice become grossly obese with age and develop several symptoms of the metabolic syndrome. In the present study, we have found a potential role of Tyk2 in the development of beige cells. Here, we show that mRNA expression of BAT-selective genes (UCP1, Cidea, Cox8b, and Elovl3) is significantly reduced in subcutaneous WAT of Tyk2-knockout (Tyk2-/-) mice compared to wild-type mice. Surprisingly, BAT-selective genes are induced in Tyk2-/- subcutaneous WAT by acute starvation. These findings suggest that Tyk2 is required for the development of beige cells under ambient conditions, and that the need for Tyk2 in beige cell development is bypassed during nutritional stress, a stimulus of the sympathetic response.
13
Costa, Rafael Menezes da. „Contribuição da interleucina 33 nas alterações vasculares mediadas pelo tecido adiposo perivascular em camundongos submetidos à dieta hiperlipídica“. Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/17/17133/tde-27042018-112307/.
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A obesidade desencadeia mudanças funcionais no tecido adiposo perivascular (PVAT), favorecendo a liberação de fatores vasoconstritores e consequente ativação de mecanismos contráteis em células vasculares. A sinalização da interleucina 33 (IL-33) via receptor ST2 é essencial para o desenvolvimento e manutenção de células T reguladoras (Tregs) no tecido adiposo visceral. Na obesidade a função das Tregs é comprometida, resultando em estresse oxidativo e inflamação do tecido adiposo. No presente estudo testamos a hipótese que dieta rica em gordura diminui os níveis e a função da IL-33 no PVAT, levando à diminuição do número e função de Tregs, estresse oxidativo e inflamação neste tecido. Camundongos deficientes para o receptor ST2 (ST2 KO) e seus respectivos controles (Balb/C) receberam dieta controle ou hiperlipídica (HFD, high fat diet) durante 18 semanas. A função vascular foi avaliada em anéis de artérias mesentéricas, em presença ou ausência de PVAT, realizando-se curvas concentração-efeito para fenilefrina. Os seguintes grupos experimentais foram analisados: Controle PVAT (-), Controle PVAT (+), HFD PVAT (-) e HFD PVAT (+). Em artérias de camundongos Balb/C que receberam dieta controle, o PVAT diminuiu a resposta contrátil a fenilefrina. No entanto, HFD promoveu perda parcial do efeito anticontrátil promovido por este tecido. Em camundongos ST2 KO que receberam dieta controle, o PVAT diminuiu a resposta contrátil a fenilefrina. No entanto, a ausência de receptores ST2 em camundongos que receberam HFD levou à perda completa do efeito anticontrátil do PVAT. Houve diminuição do número de Tregs e aumento do número de neutrófilos no PVAT de camundongos alimentados com HFD. A incubação com IL-33 recombinante não reverteu a perda do efeito anticontrátil do PVAT promovido pela HFD. Aumento nos níveis séricos e teciduais de IL-6, bem como redução nos níveis de IL-10, foram observados em animais ST2 KO. Houve aumento nos níveis de ânion superóxido no PVAT de camundongos Balb/C alimentados com HFD e a ausência do receptor ST2 potencializou este efeito. Estes dados, analisados em conjunto, indicam que HFD compromete o papel modulador do PVAT e que IL-33 via receptor ST2 tem fundamental importância para a função do PVAT nesta condição experimental.Obesity triggers functional changes in the perivascular adipose tissue (PVAT), favoring the release of vasoconstrictor factors. Interleukin-33 (IL-33) signaling, via ST2 receptor, is essential for the development and maintenance of regulatory T cells (Tregs) in the visceral adipose tissue. In obesity, Tregs function is compromised, resulting in adipose tissue inflammation. We hypothesized that high fat diet (HFD) decreases the number and function of Tregs and increases inflammation in the PVAT. Mice deficient for the ST2 receptor (ST2 KO) and their respective controls (Balb/C mice) were fed a control diet or a HFD for 18 weeks. Vascular function was evaluated in mesenteric resistance arteries, by performing concentration-effect curves to phenylephrine (PE). In Balb/C mice fed the control diet, PVAT decreased vascular PE contractions. However, a partial loss of PVAT anticontractile effect occurred in arteries from HFD-fed Balb/C mice. In arteries from ST2 KO mice fed the control diet, PVAT decreased PE contractions. However, a complete loss of PVAT anticontractile effects was observed in HFD-fed ST2 KO mice. There was a decrease in the number of Tregs and an increase in the number of neutrophils in the PVAT of mice fed the HFD. The absence of the IL-33 receptor increased IL-6 and reduced IL-10 in HFD-fed mice. There was an increase in superoxide anion levels in the PVAT of Balb/C mice fed HFD and the absence of the ST2 receptor potentiated this effect. These data show that HFD promotes PVAT dysfunction and IL-33 is fundamental to counteract HFD-induced PVAT dysfunction.
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Denton, Nathan. „Depot-specific mechanisms determining human fat distribution“. Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:d1725b54-994e-435a-ab10-832858bf041a.
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Body fat distribution is a strong determinant of human metabolic health but the mechanisms underpinning regional deposition of white adipose tissue (WAT) remain poorly understood. WAT also exhibits striking depot-specific functional properties. The aim of this project was to investigate the potential role of specific candidate genes implicated in regulating WAT development and/or function in a depot-specific manner. Cartilage oligomeric matrix protein (COMP) is an extracellular matrix protein that is highly differentially expressed between subcutaneous abdominal and gluteal WAT but has primarily been studied in the context of bone biology. WAT COMP expression was found to be significantly up-regulated in obesity; COMP expression in preadipocytes was increased by glucocorticoids; and COMP promoted adipogenesis in (immortalised) subcutaneous abdominal and gluteal preadipocytes. Building on a finding during the COMP study, bone morphogenetic protein (BMP)-2 was identified as another candidate. BMP2 exerts positive adipogenic effects in murine models and a recent genome-wide association study meta-analysis identified a significant association between BMP2 and body fat distribution. BMP2 was found to exert a pro-adipogenic effect specifically in subcutaneous abdominal preadipocytes, with this effect requiring activation of SMAD1/5/8 signalling via type 1 BMP receptors. These data identify BMP2 as a novel depot-specific regulator of human adipogenesis. Particularly lipid-laden cells were formed when conventional adipogenic medium was supplemented with fatty acids; these cells were captured, de-differentiated (DFAT) and expanded to generate immortalised abdominal and gluteal DFAT cells. These DFAT cells exhibit a greatly enhanced adipogenic potential compared to the mixed stromovascular (SVF) population from which they derive and retained an intrinsic memory of their anatomical origin. The use of DFAT cells is likely to represent a valid and enhanced model system to study various depot-specific aspects of WAT biology such as adipogenesis. Overall, the data from this thesis emphasise the striking depot-specific biology exhibited by WAT and provide novel insights into the mechanisms governing the regional distribution of WAT in humans.
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Hewitt, Michael John. „Age-related differences in human total body water relative to fat-free body mass“. Diss., The University of Arizona, 1991. http://hdl.handle.net/10150/185685.
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The objective of this investigation was to identify the appropriate isotopic fractionation factor for total body water (TBW) from ²H₂O enrichment in respiratory water vapor (RW) compared to serum (S), then to use the RW technique to estimate absolute TBW volumes and TBW relative to fat-free body mass (FFB) in three age groups (prepubescent, PP, age = 5-10 y; young adult, YA, age = 22-39 y; older adult, OA age = 65-84 y) of healthy white males and females. The effects of analytical technique (infrared spectrophotometry, IR versus isotope-ratio mass spectrometry, IRMS) and ambient relative humidity on estimates of TBW were also investigated. The composition of the FFB was estimated using a multi-component statistical model (body density, TBW and bone mineral density), and the errors associated with the traditional two-component formula for percent fat from body density were calculated. Our results demonstrated a significant (p < 0.0001) ²H₂O fractionation effect of 0.971 ± 0.005 (mean ± SEM, n = 36) for TBW from RW compared to S. Analysis by IR and IRMS were highly correlated (R² =.999) but IR values were significantly (p < 0.001) higher than IRMS. Deuterium enrichment in RW samples collected at ambient RH (∼20%) was significantly higher (Δ = 20.2 ± 4.5 ppm, mean ± SEM, p < 0.0005) than in RW samples collected at 100% RH, roughly equivalent to a 1.2 L (3.2%) difference in TBW. Total body water relative to FFB mass (W/FFB) was lower (p < 0.01) in YA males (71.0 ± 1.0%) and females (70.2 ± 1.3%) than in PP (boys = 73.1 ± 1.6%; girls = 72.2 ± 1.4%, mean ± SD). In OA, W/FFB was higher (p < 0.05) than in YA (OAM = 72.6 ± 1.1%; OAF = 72.2 ± 1.4%). The density of the FFB was 1.0996 and 1.0839 g/ml in OAM and OAF, respectively. Percent fat from density plus TBW and BMD was lower than from density alone in all groups but YA males, where it was 2.4 percent fat higher. In PP, the Siri density formula resulted in an overestimate of 5.8 ± 2.6 percent fat (mean ± SD, range = 1.4 to 13.6%). In OA females, the density formula overestimated percent fat by 4.4 ± 2.8% (range = 0 to 10.4%). In conclusion, RW corrected for isotopic fractionation will provide acceptable estimates of TBW, although the effects of analytical technique and RH should be controlled. The existence of age-related differences in FFB composition causes errors when the two-component model is used to estimate percent fat in PP and OA females.
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Guo, Yawei, und 郭雅伟. „Adiponectin limits autoimmune encephalomyelitis by suppressing the differentiation of CD4+ cells into Th17 cells“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45207690.
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Keuper, Michaela [Verfasser]. „The role of fat cell apoptosis during obesity-associated adipose tissue inflammation / Michaela Keuper“. Ulm : Universität Ulm. Fakultät für Naturwissenschaften, 2011. http://d-nb.info/1017543380/34.
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Lee, Christopher S. D. „Directing the paracrine actions of adipose stem cells for cartilage regeneration“. Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/44713.
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Current cartilage repair methods are ineffective in restoring the mechanical and biological functions of native hyaline cartilage. Therefore, using the paracrine actions of stem cell therapies to stimulate endogenous cartilage regeneration has gained momentum. Adipose stem cells (ASCs) are an attractive option for this endeavor because of their accessibility, chondrogenic potential, and secretion of factors that promote connective tissue repair. In order to use the factors secreted by ASCs to stimulate cartilage regeneration, the signaling pathways that affect postnatal cartilage development and morphology need to be understood. Next, approaches need to be developed to tailor the secretory profile of ASCs to promote cartilage regeneration. Finally, delivery methods that localize ASCs within a defect site while facilitating paracrine factor secretion need to be optimized.
The overall objective of this thesis was to develop an ASC therapy that could be effectively delivered in cartilage defects and stimulate regeneration via its paracrine actions. The general hypothesis was that the secretory profile of ASCs can be tailored to enhance cartilage regeneration and be effectively delivered to regenerate cartilage in vivo. The overall approach used the growth plate as an initial model to study changes in postnatal cartilage morphology and the molecular mechanisms that regulate it, different media treatments and microencapsulation to tailor growth factor production, and alginate microbeads to deliver ASCs in vivo to repair cartilage focal defects.
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Dimock, Hugh Douglas. „Plasma levels of insulin, glucagon and pancreatic polypeptide in relation to adiposity in genetically selected fat and lean chickens“. Thesis, McGill University, 1985. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=63169.
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Ramlugon, Sonaal. „The effect of phytocannabinoid treatment on adipogenesis and lipolysis in 3T3-L1 cells“. Thesis, Nelson Mandela Metropolitan University, 2014. http://hdl.handle.net/10948/d1021072.
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During the 1800’s cannabis use was described as a treatment for a variety of metabolic disorders but its recreational use in the twentieth century resulted in laws which made the usage of cannabis illegal despite its medicinal properties. Cannabis usage has been reported to be useful in the treatment of Type 2 diabetes but unfortunately conflicting results are often published and its mechanism of action is still unknown. The aim of this project was to investigate the effect of phytocannabinoid treatment on adipogenesis and lipolysis in 3T3-L1 cells, to unravel their mechanism of action and also to test for potential anti-diabetic properties. The studies showed that phytocannabinoid treatment promoted higher glucose uptake and significantly less fat accumulation when compared to Rosiglitazone. Rosiglitazone is an anti-diabetic drug that has recently been withdrawn from the market since its usage has been associated with severe side effects. It was also found that during the 1800’s cannabis use was described as a treatment for a variety of metabolic disorders but its recreational use in the twentieth century resulted in laws which made the usage of cannabis illegal despite its medicinal properties. Cannabis usage has been reported to be useful in the treatment of Type 2 diabetes but unfortunately conflicting results are often published and its mechanism of action is still unknown. The aim of this project was to investigate the effect of phytocannabinoid treatment on adipogenesis and lipolysis in 3T3-L1 cells, to unravel their mechanism of action and also to test for potential anti-diabetic properties. The studies showed that phytocannabinoid treatment promoted higher glucose uptake and significantly less fat accumulation when compared to Rosiglitazone. Rosiglitazone is an anti-diabetic drug that has recently been withdrawn from the market since its usage has been associated with severe side effects. It was also found that phytocannabinoid treatment was able to reverse the insulin-resistant state of 3T3-L1 cells. The study indicates that the mechanism of action occurs at the mitochondrial level where enzymes such as succinate dehydrogenase and glycerol-3-phosphate dehydrogenase are modulated thereby affecting oxidative phosphorylation involved in the respiratory chain. In addition the effect observed with phytocannabinoid treatment is time dependent and affects the cells differently at different developmental stages. Therefore it can be concluded that phytocannabinoid treatment not only helps to maintain the balance between adipogenesis and lipolysis in 3T3-L1 cells but its use may also be helpful in the treatment of Type 2 diabetes and/or obesity-related insulin resistance.phytocannabinoid treatment was able to reverse the insulin-resistant state of 3T3-L1 cells. The study indicates that the mechanism of action occurs at the mitochondrial level where enzymes such as succinate dehydrogenase and glycerol-3-phosphate dehydrogenase are modulated thereby affecting oxidative phosphorylation involved in the respiratory chain. In addition the effect observed with phytocannabinoid treatment is time dependent and affects the cells differently at different developmental stages. Therefore it can be concluded that phytocannabinoid treatment not only helps to maintain the balance between adipogenesis and lipolysis in 3T3-L1 cells but its use may also be helpful in the treatment of Type 2 diabetes and/or obesity-related insulin resistance.
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Goff, Kayleen Adams. „Percent Body Fat and Fat Distribution are Not Associated with Carotid Artery Intima-media Thickness in Healthy Middle-aged Women“. Diss., CLICK HERE for online access, 2008. http://contentdm.lib.byu.edu/ETD/image/etd2492.pdf.
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Thomas, Kathryn S. „Dietary fiber intake and body fat gain : a prospective cohort study of middle-aged women /“. Diss., CLICK HERE for online access, 2007. http://contentdm.lib.byu.edu/ETD/image/etd1897.pdf.
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Ronkainen, J. (Justiina). „Role of Fto in the gene and microRNA expression of mouse adipose tissues in response to high-fat diet“. Doctoral thesis, Oulun yliopisto, 2016. http://urn.fi/urn:isbn:9789526213453.
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Abstract Obesity is associated with greater risk of several diseases, such as type 2 diabetes and metabolic syndrome. Single nucleotide polymorphisms (SNP) within the fat mass- and obesity-associated gene FTO are robustly associated with increased body mass index (BMI) in several age and ethnic groups. Studies with transgenic mice support a mechanistic role for FTO protein in energy metabolism. Fto-deficient mice are leaner than wild-type and overexpression of Fto leads to obese phenotype; however, the precise mechanism of FTO action in the control of BMI has remained obscure. Fto mRNA is most abundant in the brain while high expression is present also in white and brown adipose tissues (WAT and BAT, respectively). WAT stores the nutritional energy and BAT dissipates it to produce heat. Furthermore, these organs participate in a complex endocrine network affecting the whole body metabolism, which is more or less disrupted in obesity. In the browning process, white adipocytes begin to manifest brown characteristics. MicroRNAs (miRNA) are small RNA molecules, which fine-tune post-transcriptionally the expression of genes important in several cellular processes, including WAT and BAT differentiation and browning of WAT. FTO has been shown to participate in these processes as well as miRNA regulation. The current study used a new Fto-deficient mouse model to reveal deeper insights into the role of Fto on genes affecting WAT and BAT differentiation and function, as well as WAT browning. Furthermore, the effects of Fto on the miRNA regulation in WAT browning and BAT were investigated. Our results supported a role for Fto in adipose tissue. Fto-deficient mice were resistant to diet-induced obesity and their WAT and BAT adipocytes did not become hypertrophic similar to wild-type on high-fat diet. Furthermore, the expression of genes affecting adipose tissue differentiation and function was altered in Fto-deficient WAT and BAT, especially after high-fat diet, and the changes may be mediated via altered miRNA expression. Fto-deficient WAT was more susceptible to browning, which in part contributed to the lean phenotype of these mice. Current study supported a role for Fto in whole body metabolism and adaptation of adipose tissue to changes in dietary environmentTiivistelmä Lihavuus on toistuvasti yhdistetty useisiin liitännäissairauksiin, kuten tyypin 2 diabetekseen ja metaboliseen oireyhtymään. FTO-geenissä (fat mass- and obesity-associated) esiintyvien yhden nukleotidin muutoksien (single nucleotide polymorphia, SNP) on useissa ikä- ja etnisissä ryhmissä raportoitu liittyvän korkeampaan painoindeksiin ihmisillä. Muuntogeenisillä hiirillä tehdyt tutkimukset tukevat FTO:n mekanistista roolia energia-aineenvaihdunnassa, sillä Fto-poistogeeniset hiiret ovat villityypin hiiriä laihempia ja sen yliekspressio johtaa ylipainoon. FTO:n tarkka rooli painon säätelyssä on kuitenkin vielä epäselvä. Fto:ta tuotetaan eniten aivoissa, mutta myös valkoisessa ja ruskeassa rasvassa. Valkoinen rasva varastoi ravinnosta saatavan energian ja ruskea hajottaa sitä lämmöntuotantoon. Näillä kudoksilla on lisäksi tärkeä rooli energia-aineenvaihdunnan monimutkaisessa verkostossa. Valkoisen rasvakudoksen ruskettumisprosessissa valkoiset rasvasolut alkavat muistuttaa ruskeita rasvasoluja. Mikro-RNA:t (miRNA) ovat pieniä RNA-juosteita, jotka hienosäätävät geenien ekspressiota transkription jälkeen ja vaikuttavat useisiin solun tärkeisiin tapahtumiin, myös valkoisen ja ruskean rasvasolun erilaistumiseen ja ruskettumiseen. FTO osallistuu näihin prosesseihin sekä miRNA-säätelyyn. Tämän tutkimuksen tavoitteena oli selventää Fto:n roolia valkoisen ja ruskean rasvakudoksen erilaistumisessa ja toiminnassa Fto-poistogeenisen hiirimallin avulla. Lisäksi selvitettiin Fto:n vaikutuksia valkoisen rasvan ruskettumiseen ja ruskean rasvan toimintaan osallistuvien miRNA:iden säätelyyn. Tulokset tukivat FTO:n roolia rasvakudoksessa. Fto-poistogeeniset hiiret eivät lihoneet rasvaisella ruokavaliolla eivätkä niiden rasvasolut varastoineet rasvaa yhtä paljon kuin villityypin hiirillä rasvaisen ruokavalion jälkeen. Lisäksi Fto-poistogeenisen rasvakudoksen erilaistumiseen ja toimintaan liittyvien geenien esiintyvyys muuttui erityisesti rasvaisella ruokavaliolla. Nämä muutokset voivat osittain selittyä muuttuneella miRNA-säätelyllä. Tulokset viittasivat siihen, että Fto-poistogeeninen valkoinen rasvakudos oli alttiimpaa ruskettumiselle, mikä osaltaan vaikutti Fto-poistogeenisten hiirten laihuuteen. Tutkimus tuki Fto-geenin roolia energia-aineenvaihdunnan säätelyssä sekä rasvakudoksen mukautumisessa ruokavalion muutoksiin
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Centurión, Patricio, Ronald Gamarra, Gonzalo Caballero, Paul Kaufmann und Pia Delgado. „Optimizing harvesting for facial lipografting with a new photochemical stimulation concept: One STEP technique™“. Springer Science and Business Media Deutschland GmbH, 2020. http://hdl.handle.net/10757/655506.
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Background: Facial fat grafting for rejuvenation is one of the most popular facial aesthetic procedures in plastic surgery. It is always challenging and since there are a lot of techniques for adipose tissue (AT) harvesting, there are no standard procedures that guarantee natural and long-lasting results. We developed the selective tissue engineering photo stimulation technique (One STEP™) in which we used a novel infrared 1210-nm wavelength laser diode for fat preserved harvesting and direct fat injection that we named PicoGraft™, with no fat manipulation. Methods: This is a retrospective descriptive study in which we included all senior author’s patients that got facial fat grafting using the One STEP™ technique. We compared the AT aspirated, after laser emission (STEP-PicoGraft) and the standard assisted liposuction samples (SAL) in cultures. We study the mitochondrial activity of the ASC between STEP and SAL in fresh samples and after 24 h. The evaluation of the results included subjective changes regarding wrinkles, grooves, palpebral bags, hyperchromic spots, and fat hypotrophy of our patients. Results: Between July 2013 and May 2018, a total of 245 patients underwent facial fat grafting using this novel technique. We observed adipocytes preserved after STEP harvesting comparing morphologic changes in SAL samples with a high concentration of inflammatory particles in cultures. ASC mitochondrial activity shows an important difference of more than 7 times in STEP samples in fresh analysis that increase 12 times in 24 h. The subjective results show a good improvement in the periorbital area. The changes on the skin and subcutaneous tissue are seen from the second month and continue to improve up to 12 months. Conclusions: Facial fat grafting using the PicoGraft™ obtained by One STEP™ technique gives excellent volumetric and regenerative results in a single treatment without volumetric hypercorrection, and it is a good alternative for facial rejuvenation. The fat graft obtained with this novel technique is homogenous, without lumps, and has high concentration of viable stimulated ADSC and a high number of viable adipocytes. Level of evidence: Level III, therapeutic study.Revisión por pares
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Kaiyala, Karl John. „Effects of high fat feeding on determinants of glucose tolerance and brain insulin delivery in dogs /“. Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/9140.
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Chang, Junlei, und 畅君雷. „Regulation of vascular integrity by eNOS and adiponectin: a novel role of endothelial progenitor cells“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47244276.
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Background and objectives:
Circulating endothelial progenitor cells (EPCs) play an essential role in maintaining vascular integrity and preventing endothelial dysfunction. Decreased circulating EPC levels are frequently observed in various cardiovascular risks, including aging and diabetes. Endothelial nitric oxide synthase (eNOS) and adiponectin exert their vasculo-protective effects by directly targeting the key components of the vascular system, such as endothelial cells and smooth muscle cells. Both eNOS and adiponectin have been implicated in the mobilization and in vitro functions of EPCs. However, whether and how circulating EPCs are involved in eNOS and adiponectin-mediated vascular protection remain unclear.
The objective of this study is to investigate the role of circulating EPCs in eNOS and adiponectin-mediated regulation of vascular integrity after arterial injury under both physiological and pathophysiological conditions, and to elucidate the underlying mechanisms involved.
Key findings:
1. Modulation of eNOS activity in vivo by replacing the serine 1176 (S1176) with an aspartate (S1176D mutation or Dki) to mimic phosphorylation or with an alanine (S1176A mutation or Aki) to render it unphosphorylatable altered reendothelialization and subsequent endothelial function after arterial injury in mice.
2. eNOS S1176D mutation increased the number of circulating EPCs and their incorporation into regenerated endothelium, whereas eNOS S1176A or knockout (KO) impaired the mobilization and reendothelializing capacity of circulating EPCs after injury.
3. eNOS S1176D elevated circulating EPCs by promoting the proliferation and differentiation of bone marrow hematopoietic stem cells (HSCs) into EPCs and by inhibiting apoptosis of circulating EPCs.
4. Adiponectin deficiency in mice resulted in progressive decrease of circulating EPCs with aging. Systemic administration of recombinant adiponectin reversed the decreased EPCs number in adiponectin KO mice. In db(-/-) diabetic mice, adiponectin deficiency further reduced circulating EPCs number and subsequent reendothelialization after injury. Rosiglitazone (Rosi), an antidiabetic drug, induced an upregulation of EPCs number and improved reendothelialization, which were partially abolished in the absence of adiponectin.
5. In cultured EPCs, adiponectin significantly inhibited high glucose-induced premature senescence, whereas its effects on proliferation and apoptosis were not evident. High glucose instigated EPCs senescence by increasing the intracellular accumulation of reactive oxygen species (ROS), activation of p38 MAPK and expression of p16INK4A, whereas all these changes could be abolished by adiponectin through adenosine monophosphate (AMP)-activated protein kinase (AMPK) and cyclic AMP (cAMP)/protein kinase A (PKA)-dependent pathways.
6. Compared to cells from db(-/-) diabetic mice, bone marrow EPCs isolated from db(-/-) plus adiponectin double KO (DKO) mice were more susceptible to high glucose-evoked senescence, which were abrogated by adiponectin in vitro. Importantly, chronic administration of adiponectin or the anti-oxidant N-acetylcysteine (NAC) prevented both aging and diabetes-associated elevation of p16INK4A and decline of circulating EPCs in DKO mice.
Conclusions:
Collectively, the current study demonstrates that circulating EPCs are actively involved in the vasculo-protective effects of both eNOS and adiponectin under physiological and pathological conditions. These findings enrich our knowledge of the versatile functions of eNOS and adiponectin in vascular protection and provide solid scientific evidence supporting the use of eNOS and adiponectin as possible therapeutic targets for cardiovascular diseases.published_or_final_version
Medicine
Doctoral
Doctor of Philosophy
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Chow, Hei-man. „The effects of ageing and high-fat diet on the gene expression of adrenomedullin and its receptor components in rat skeletal muscles and adipose tissues“. Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38767016.
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Behrman, Roger L. „The effects of dietary fat and age on adipose tissue composition and fatty acid synthesis levels in strain A/ST mice“. Virtual Press, 1990. http://liblink.bsu.edu/uhtbin/catkey/722436.
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Differences in fatty acid distributions in adipose tissue and fatty acid synthetase levels in the liver were determined in Strain A/ST mice of different ages and diets. Since fatty acids have been found to be influential in many disease processes such as heart disease and cancer, which become more prevalent with increasing age, it is important to understand the processes of fat metabolism and changes that occur during the life-stage of senescence. Fatty acid distributions were determined by gas liquid chromatography and fatty acid synthetase (FAS) activities by spectrophotometry.The data from FAS analyses indicated that the mice fed the highfat palmitic acid and low-fat corn oil diets were similar to previous research. The mice fed the stearic acid diets had FAS activity that was affected in a very different manner than other high-fat diets.The results of this study also indicated that aging does not significantly effect the distribution of fatty acids in the adipose tissue of experimental mice. Weight gain in the middle age mice appears to be the result of an increase in all types of fatty acids and not just increased storage of one or a few types.Department of Biology
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Chow, Hei-man, und 周熙文. „The effects of ageing and high-fat diet on the gene expression of adrenomedullin and its receptor components in rat skeletal muscles andadipose tissues“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B38767016.
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Wassef, Hanny. „Synthesis and secretion of apoC-I and apoE by human SW872 liposarcoma cells“. Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82447.
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Apolipoprotein C-I (apoC-I) plays an important role in the metabolism of plasma triglyceride levels and cholesterol metabolism. Little is known about the regulation of apoC-I production by human adipocytes. Aim. To investigate the effect of different tissue culture conditions on the synthesis and secretion of apoC-I and apoE in human SW872 liposarcoma cells and to study the effects of apoC-I overexpression in these same cells. Methods. SW872 cells were grown in DMEM/F-12 (3:1, v/v). QPCR was used to quantify mRNA synthesis. ELISAs were used to quantify intracellular and extracellular proteins. Colorimetric reaction kits were used to analyze intracellular cholesterol and triglyceride concentrations. Results . Maturation experiments revealed that after 17 days in culture, SW872 cells contained significantly more cholesterol (100%) and triglyceride (3-fold). Cell maturation was associated with significantly higher levels of apoE mRNA (+200%) but not apoC-I mRNA (-50%). The cells secreted more apoC-I (+110%) and apoE (+340%). Cellular apoC-I increased 620% and apoE increased 1540%. Treatment of cells during maturation with insulin (0, 10 or 1000 nM) significantly reduced the secretion of apoC-I and apoE (-14% and -56%, respectively) and intracellular apoC-I and apoE (-10% and -12%, respectively. Overexpression of apoC-I in SW872 cells resulted in increased cell number (+70%) and decreased lipids per cell (-32% triglyceride, -36% cholesterol) as compared to controls. Conclusion. These results suggest that apoC-I and apoE production is differentially regulated at the transcriptional level in adipocytes and that apoC-I and apoE play a role in the maturation of human adipocytes and may have an important role in mediating or regulating cell lipid accumulation. As well, overexpression of apoC-I in SW872 cells impedes cellular lipid accumulation and stimulates cellular proliferation.
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Tran, Khanh-Van T. „Origin of White and Brown Adipose Cells From Vascular Endothelium: A Dissertation“. eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/591.
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Obesity is associated with insulin resistance, dyslipidemia, and cardiovascular disease. The current obesity epidemic is the result of surplus energy consumption. Excess energy is stored in expanding adipose tissue. Adipose tissue growth entails the enlargement of existing adipocytes, the formation of new fat cells from preexisting progenitors, and the coordinated development of supporting vasculature. Identifying adipocyte progenitors and the mechanism of adipose tissue expansion is crucial for the development of new strategies to combat obesity and its complications.
Though important progress has been made towards understanding the developmental origin of adipocytes, the identities of adipocyte progenitors are still not completely known. The main objective of this study is to determine whether endothelial cells of the adipose tissue can give rise to new adipocytes. Our results indicate that murine endothelial cells of adipose tissue are pluripotent and can potentially give rise to preadipocytes. Lineage tracing experiments using the VE-Cadherin-Cre transgenic mouse reveal localization of reporter genes in endothelial cells, preadipocytes and white and brown adipocytes. Moreover, capillary sprouts from human adipose tissue, which have predominantly endothelial cell characteristics, are found to express Zfp423, a preadipocyte determination factor. In response to PPARγ activation, endothelial characteristics of sprouting cells are progressively lost, and cells form structurally and biochemically defined adipocytes. Taken together, our data support an endothelial origin of a population of adipocytes. The ability of the vascular endothelium to give rise to adipocytes may explain how angiogenesis and adipogenesis can be temporally and spatially coordinated.
Analysis of BAT and WAT revealed that adipose depots have distinct compositions of adipocyte progenitors. Of the CD45-CD29+Sca1+CD24+ progenitor population, only 17% and 52% express VE-Cadherin in WAT and BAT, respectively. Our data show that the number of these specific progenitors in BAT and WAT are highly variable and suggest that a considerable number of adipocytes progenitors may have a non-endothelial cell origin. Differences in composition and types of adipocyte progenitors may explain the differences in the adipocytes phenotypes that we observe in discrete depots.
In brief, we find that the vascular endothelium gives rise to a population of brown and white fat cells, and that the number of endothelial-derived adipocyte progenitors residing in BAT and WAT is highly variable. These results expand our current understanding of adipose tissue growth, and, we hope, will accelerate the development of treatments for obesity-related complications.
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Foster, Michelle Tranace. „Central Nervous System Regulation of Fat Cell Lipid Mobilization: The Role of the Sympathetic Nervous System“. Digital Archive @ GSU, 2006. http://digitalarchive.gsu.edu/biology_diss/2.
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Obesity is a growing disorder in the United States, affecting over 60% of the population. We previously defined sympathetic nervous system (SNS) outflow from brain to white adipose tissue (WAT) using a viral transneuronal tract tracer. SNS innervation of WAT is the principle initiator of lipolysis, whereas decreases in sympathetic drive promote lipid accumulation. Which of the many origins of SNS outflow from brain to WAT results in SNS-mediated changes in lipid mobilization (increases in drive) or accumulation (decrease in drive) is unknown. Previous research indicates that sympathetic denervation blocks lipid mobilization; thus, rostral sites in the neuroaxis connected to WAT via the SNS may promote WAT lipid mobilization. The hypothalamic paraventricular nucleus (PVN) may play a role via its descending projections to the intermediolateral horn of the spinal cord. Therefore, the consequences of PVN lesions (PVNx) on WAT mobilization or accumulation were tested. PVNx resulted in increased lipid accumulation, indicated by increases in retroperitoneal (RWAT) , epididymal (EWAT) , and inguinal WAT (IWAT) pad masses, in fed hamsters, but PVNx did not block fasting (56 h)-induced lipid mobilization. Because adrenal medullary catecholamines, especially epinephrine, also play a minor role in lipid mobilization, we tested the contribution of catecholamine release on lipid mobilization through adrenal demedullation (ADMEDx), with and without PVNx, and found fastinginduced lipid mobilization was not blocked. There was, however, a suggestion that distal denervation of IWAT, with and without ADMEDx, partially blocked lipid mobilization. In addition, evidence suggests SNS also may be an important controller of fat cell proliferation. Surgical denervation of WAT triggers increases in fat cell number (FCN), but have not determined if this FCN increase is due to preadipocyte proliferation or differentiation of preadipocytes into mature fat cells. We also have not demonstrated what role sensory innervation may have in regulating white adipocyte proliferation. Therefore, the role of WAT sympathetic or sensory innervation on adipocyte proliferation was tested. The SNS but not sensory denervation triggered bona fide proliferation as indicated by bromodeoxyuridine plus AD3, a specific adipocyte membrane protein, colabeling. These and previous data suggest that the SNS plays a role in regulating adiposity.
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Ribeiro, Gesiane [UNESP]. „Células-tronco mesenquimais de equinos: isolamento, cultivo e caracterização“. Universidade Estadual Paulista (UNESP), 2009. http://hdl.handle.net/11449/101114.
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As células-tronco da linhagem mesenquimal representam uma fonte promissora para o tratamento de injúrias do sistema músculo-esquelético de equinos atletas. Objetivou-se com este trabalho avaliar técnicas de coleta e isolamento de células-tronco mesenquimais em equinos, determinar a caracterização morfológica e fenotípica e avaliar o comportamento celular sob diferentes condições de cultivo. Cinco cavalos foram submetidos à coleta de medula óssea do esterno e de tecido adiposo da região glútea. As amostras foram processadas para o isolamento de células mononucleares e cultivadas em dois tipos de meios de cultivo. No vigésimo quinto dia, foi adicionado TGF-β1, mantendo um grupo controle para cada meio. As técnicas de coleta e processamento foram avaliadas por meio de fatores como facilidade de obtenção, viabilidade celular e número de células obtidas. Características morfológicas qualitativas foram avaliadas semanalmente mediante observação das colônias por microscopia óptica de luz invertida. Características fenotípicas foram avaliadas testando-se marcadores de superfície. Os efeitos do TGF-β1 sobre as culturas de células foram determinados por meio de avaliação citoquímica, número de unidades formadoras de colônia e porcentagens de apoptose e necrose. Foram observadas diferenças entre as amostras em fatores como a viabilidade celular após descongelamento, formação de colônias e relação entre necrose e apoptose em meios de cultivo diferentes. O TGF-β1 apresentou um efeito indutor de apoptose e estimulou a formação de colônias e a produção de proteoglicanas sulfatadas confirmando o efeito condrogênico
Mesenchymal stem cells could be a new treatment for healing musculo-skeletal injuries of equine athlete. The objectives of this study were: to analyze the harvest and isolation techniques of equine mesenchymal stem cells, to determine morphological and phenotypical characterization and to evaluate cellular behavior in different culture conditions. Five horses had sternal aspirates bone marrow and croup fat tissue harvest. Both of them harvested materials was processed for mononuclear cells isolation and cultivate in two different kinds of culture medium. Twenty-five days later TGF-β1 was add in both culture mediums, remains a control group for each one. The harvest and process techniques were evaluated through some factors like: easily of harvest, cellular viability and cellular number. Morphological qualitative characteristics were described weekly by culture microscopy observation. Phenotypical characteristics were evaluated testing cluster markers. The effects of TGF-β1 on the cells cultures were determined by histological evaluation, number of unit forming colony and relation between necrosis and apoptosis. Differences between bone marrow and fat tissue cells were observed in some factors like: cellular viability after freezing, unity colony forming and relation between necrosis and apoptosis in different mediums culture. TGF-β1showed apoptosis inductor effect and stimulated the unit forming colony and sulfated proteoglicans production confirming the chondrogenic effect
34
MacIntyre, Terence M. „Acetyl CoA carboxylase, adipocyte P2, lipoprotein lipase, and hormone-sensitive lipase mRNA levels in the ovine adipose tissues and their relationship with carcass fat“. Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ49399.pdf.
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Qadan, Maha Ahmad. „Sourcing and Modulation of the Fate of Connective Tissue Progenitors“. Kent State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1479416651140376.
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36
Hsiao, Wen-Yu. „The Lipid Handling Capacity of Subcutaneous Fat Requires mTORC2 during Development“. eScholarship@UMMS, 2020. https://escholarship.umassmed.edu/gsbs_diss/1087.
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Overweight and obesity are associated with Type 2 Diabetes, non-alcoholic fatty liver disease, cardiovascular disease and cancer, but all fat is not equal as storing excess lipid in subcutaneous white adipose tissue (SWAT) is more metabolically favorable than in visceral fat. Here, we uncover a critical role for mTORC2 in setting SWAT lipid handling capacity. We find that subcutaneous white preadipocytes differentiating without the essential mTORC2 subunit Rictorexpress mature adipocyte markers but develop a striking lipid storage defect. In vivo,this results in smaller adipocytes, reduced tissue size, lipid re-distribution to visceral and brown fat, and sex-distinct effects on systemic metabolic fitness. Mechanistically, mTORC2 promotes transcriptional upregulation of select lipid metabolism genes controlled by PPARgand ChREBP. These include genes that control lipid uptake, synthesis, and degradation pathways as well as Akt2, the gene encoding its substrate and insulin effector. Finally, we reveal a potential novel mTORC2 target, ACSS2, which might control intracellular acetyl-CoA availability and regulate metabolic gene expression by altering histone modification in white adipocytes. Exploring this pathway may uncover strategies to promote safe lipid storage and improve insulin sensitivity.
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Murrieta, Charles M. „Lipogenic enzyme mRNA of milk and adipose tissue of lactating beef cows and their calves influence of day of lactation, maternal dietary fat supplementation, and body condition score /“. Laramie, Wyo. : University of Wyoming, 2007. http://proquest.umi.com/pqdweb?did=1338900371&sid=1&Fmt=2&clientId=18949&RQT=309&VName=PQD.
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38
Tunn, Ruth Elizabeth. „Expression of two-pore channels in mammalian primary cells and tissues, and their role in adipose tissue formation and function“. Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:6c0b970d-6133-4752-987a-e21f6e2dc69c.
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Two-pore channels (TPCs, gene name Tpcn) have recently been identified as endolysosomal cation channels modulated by the potent calcium (Ca2+) releasing messenger nicotinic acid adenine dinucleotide phosphate (NAADP). Gene knockout (KO) and RNA knockdown studies have implicated TPCs in fundamental cellular processes, including secretion, of insulin in pancreatic islets, and differentiation, of skeletal myoblasts and osteoclasts. Investigations of Tpcn1 and Tpcn2 mRNA expression have indicated widespread tissue distribution, but a lack of suitable antibodies has impeded study of the endogenous proteins. In this study, an anti-TPC1 antibody was purified from immune sera and used in immunoblotting investigations to demonstrate TPC1 protein expression in a wide range of mouse tissues, with highest expression levels observed in kidney, liver and adipose tissue. Endogenous mouse TPC1 was demonstrated to be glycosylated, with apparent differences in the extent of glycosylation in different tissues based on the indicated molecular weight before and after treatment with a deglycosylating enzyme, which may have implications for the functional regulation of channel activity. Given the increasing prevalence of type 2 diabetes and obesity, an understanding of the molecular basis of glucose homeostasis and adipose tissue formation and function is an important scientific goal. Tpcn KO mice have been developed; in both Tpcn1 KOs and Tpcn2 KOs, impaired pancreatic β-cell Ca2+ signalling and reduced insulin secretion from the whole pancreas were demonstrated. However, the whole-animal phenotype has not been extensively researched. In this study, intraperitoneal glucose tolerance tests were conducted in Tpcn KO mice. These indicated that glucose homeostasis was not significantly affected in Tpcn2 KOs or Tpcn1/2 double KOs (DKOs), and only mildly impaired in Tpcn1 KOs, despite the defects previously observed at the cellular and tissue level. In addition, body composition was investigated in Tpcn1 KO, Tpcn2 KO and Tpcn1/2 DKO animals using magnetic resonance spectroscopy and time domain-nuclear magnetic resonance. Single Tpcn KOs were found to have lower adipose tissue levels as a percentage of body composition, while Tpcn1/2 DKOs were shown to have increased bodyweight but normal body composition. To investigate potential roles for TPCs in adipose tissue formation, Tpcn expression during adipogenesis was investigated using an in vitro multipotent mesenchymal stem cell line model of adipogenic differentiation. Tpcn2 mRNA levels were demonstrated by quantitative PCR to be transiently increased during the early stages of adipogenic differentiation, and cyclic AMP (cAMP) was identified as the factor that induced this upregulation. Lentiviruses were developed to express fluorescently-tagged TPCs, and overexpression of TPC2 was demonstrated to partially overcome the requirement for the cAMP-inducing agent in the medium used for the induction of adipogenesis. Collectively, these data suggest that TPCs may play a role in the formation and/or function of adipose tissue.
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Ribeiro, Gesiane. „Células-tronco mesenquimais de equinos : isolamento, cultivo e caracterização /“. Jaboticabal : [s.n.], 2009. http://hdl.handle.net/11449/101114.
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Orientador: José Corrêa de Lacerda NetoBanca: Ana Liz Garcia Alves
Banca: Cristina de Oliveira Massoco
Banca: Silvana Martinez Baraldi Artoni
Banca: Marcia Rita Fernandes Machado
Resumo: As células-tronco da linhagem mesenquimal representam uma fonte promissora para o tratamento de injúrias do sistema músculo-esquelético de equinos atletas. Objetivou-se com este trabalho avaliar técnicas de coleta e isolamento de células-tronco mesenquimais em equinos, determinar a caracterização morfológica e fenotípica e avaliar o comportamento celular sob diferentes condições de cultivo. Cinco cavalos foram submetidos à coleta de medula óssea do esterno e de tecido adiposo da região glútea. As amostras foram processadas para o isolamento de células mononucleares e cultivadas em dois tipos de meios de cultivo. No vigésimo quinto dia, foi adicionado TGF-β1, mantendo um grupo controle para cada meio. As técnicas de coleta e processamento foram avaliadas por meio de fatores como facilidade de obtenção, viabilidade celular e número de células obtidas. Características morfológicas qualitativas foram avaliadas semanalmente mediante observação das colônias por microscopia óptica de luz invertida. Características fenotípicas foram avaliadas testando-se marcadores de superfície. Os efeitos do TGF-β1 sobre as culturas de células foram determinados por meio de avaliação citoquímica, número de unidades formadoras de colônia e porcentagens de apoptose e necrose. Foram observadas diferenças entre as amostras em fatores como a viabilidade celular após descongelamento, formação de colônias e relação entre necrose e apoptose em meios de cultivo diferentes. O TGF-β1 apresentou um efeito indutor de apoptose e estimulou a formação de colônias e a produção de proteoglicanas sulfatadas confirmando o efeito condrogênico
Abstract: Mesenchymal stem cells could be a new treatment for healing musculo-skeletal injuries of equine athlete. The objectives of this study were: to analyze the harvest and isolation techniques of equine mesenchymal stem cells, to determine morphological and phenotypical characterization and to evaluate cellular behavior in different culture conditions. Five horses had sternal aspirates bone marrow and croup fat tissue harvest. Both of them harvested materials was processed for mononuclear cells isolation and cultivate in two different kinds of culture medium. Twenty-five days later TGF-β1 was add in both culture mediums, remains a control group for each one. The harvest and process techniques were evaluated through some factors like: easily of harvest, cellular viability and cellular number. Morphological qualitative characteristics were described weekly by culture microscopy observation. Phenotypical characteristics were evaluated testing cluster markers. The effects of TGF-β1 on the cells cultures were determined by histological evaluation, number of unit forming colony and relation between necrosis and apoptosis. Differences between bone marrow and fat tissue cells were observed in some factors like: cellular viability after freezing, unity colony forming and relation between necrosis and apoptosis in different mediums culture. TGF-β1showed apoptosis inductor effect and stimulated the unit forming colony and sulfated proteoglicans production confirming the chondrogenic effect
Doutor
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May, Stéphanie [Verfasser], Thomas [Akademischer Betreuer] Skurk und Dirk [Akademischer Betreuer] Haller. „Influence of adipogenesis and high fat diet on the development of cell stress markers in adipose tissue / Stephanie May. Gutachter: Dirk Haller ; Thomas Skurk. Betreuer: Thomas Skurk“. München : Universitätsbibliothek der TU München, 2013. http://d-nb.info/104744092X/34.
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Monelli, Erika. „Deciphering the role of endothelial cells in the regulation of physiological and pathological white adipose tissue remodelling“. Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/572073.
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In response to nutritional variation, white adipose tissue (WAT) undergoes a physiological remodelling that involves qualitative and quantitative changes in resident cells and is coordinated with angiogenesis. In a condition of chronic over nutrition WAT expansion is associated to insufficient vascularisation which in turn leads to local hypoxia, inflammation and adipocytes death (hallmark of obesity). Currently, enhanced WAT angiogenesis is believed to be a promising intervention to ameliorate obesity associated metabolic dysfunctions. However, we still lack understanding of the cell intrinsic function of endothelial cells in WAT remodelling. Here we take advantage of our mouse model of PTEN (a dual lipid/protein phosphatase that counterbalance the
activity of PI3K) deletion in ECs to promote vessel growth, in a cell autonomous manner. To this end, we crossed Ptenflox/flox mice with PdgfbiCreERT2 transgenic mice that express a tamoxifen-inducible Cre recombinase in ECs; 4-hydroxytamoxifen was administered in vivo at postnatal day 1 (P1) and P2 to activate Cre expression.
Increased ECs proliferation, induced by PTEN loss, promotes vascular hyperplasia exclusively in WAT and leads to a progressive loss of WAT mass. PTEN null ECs undergo a metabolic switch towards an oxidative metabolism; in vivo inhibition of - oxidation is sufficient to revert both vascular hyperplasia and loss of WAT mass. Enhanced adipose vascularisation prevents from high fat diet induced WAT hypertrophy, limits body weight gain and improves glucose tolerance. Taken together our results suggest that, under obesogenic stimuli, more functional ECs prevent unhealthy WAT expansion and consequently the onset of obesity related comorbidity.
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Castro, Natalie Carolina de. „O volume celular do adipócito contribui para a heterogeneidade funcional do tecido adiposo branco“. Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/42/42137/tde-20052010-145421/.
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O tecido adiposo já foi considerado um tecido metabolicamente pouco ativo, no entanto, os mais recentes avanços mostram que ele desempenha uma função importante no controle da homeostase energética. Baseado neste conceito, este trabalho objetivou caracterizar o perfil morfológico e metabólico de adipócitos isolados de três diferentes coxins adiposos, subcutâneo, peri-epididimal, retro-peritoneal (SC, PE e RP respectivamente). Os adipócitos dos diferentes coxins foram coletados e submetidos a análise morfológica, aos ensaios metabólicos e análise da expressão de enzimas envolvidas no metabolismo lipídico e glicídico. Os resultados mostraram diferença estatisticamente significativa no volume dos adipócitos das três regiões entre si (p<0,05), maior capacidade lipogênica dos adipócitos RP. Paralelamente, o tecido SC, mostrou maior expressão de enzimas envolvidas na via lipogênica (p< 0,05; SC vs PE e RP).The adipose tissue was considered to be a little active metabolic tissue, however, the most recent advances show that it plays an important function in the control of the energy homostasis. Based on this concept, this work aimed to characterize the morphology and metabolism of isolated adipocytes of three different depots, like: subcutaneous, periepididymal, retroperitoneal (SC, PE and RP) . The adipocytes of the different depots had been collected and submitted to morphologic analysis, metabolic assays and to analysis of the enzymes expressions involved on lipids and glucose metabolism. The results showed statistical significant difference on volume of the adipocytes among the three different depots (p< 0, 05), high lipogenic capacity of RP adipocytes and higher expression of proteins involved in lipogenic patways of SC adipocytes (p<0, 05).
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Aikio, M. (Mari). „Novel roles for basement membrane collagens:isoform-specific functions of collagen XVIII in adipogenesis, fat deposition and eye development, and effects of the collagen IV-derived matricryptin arresten on oral carcinoma growth and invasion“. Doctoral thesis, Oulun yliopisto, 2013. http://urn.fi/urn:isbn:9789526203188.
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Abstract Collagen XVIII is an evolutionarily conserved, ubiquitously-expressed basement membrane (BM) proteoglycan produced in three isoforms, the individual roles of which are largely unknown. The physiological in vivo roles of these collagen XVIII isoforms are studied here using novel genetically modified mouse strains deficient in either the short or the medium/long isoforms of the molecule. In addition, the effects of keratin-14-driven overexpression of the thrombospondin-1 (Tsp-1) –like domain, which is common to all three collagen XVIII isoforms, are studied. The findings underline the importance of the short collagen XVIII isoform in the eye, as its absence was sufficient to cause the aberrant vascularisation of the retina previously reported in mice lacking all isoforms of collagen XVIII. In addition, an excess of the collagen XVIII Tsp-1 domain led to serious eye abnormalities, possibly by interfering with the functions of the full-length collagen XVIII produced in mice. Collagen XVIII was also shown to contribute to adipogenesis in an isoform-specific manner, in that a lack of the medium/long isoforms of collagen XVIII led to impaired adipocyte maturation and the subsequent reduction in the adipocyte number induced liver steatosis and hypertriglyceridaemia. Hence this work establishes a new extracellular matrix ECM-directed mechanism contributing to control over the multistep adipogenesis programme and points to the functional consequences of its impairment for ectopic fat deposition. The enzymatic remodelling of ECM components results in molecules with novel biological activities. Arresten is a collagen IV(α1)-derived fragment with anti-angiogenic properties which was originally described as not having any direct anti-tumour effects on cancer cells themselves. The present data revealed novel inhibitory roles for arresten in oral squamous carcinoma cell proliferation, survival, motility and invasion. Since arresten is a potent inhibitor of angiogenesis, the data generated here further underline the possibility for using it as a therapeutic agent in cases of cancerTiivistelmä Kollageeni XVIII on tyvikalvojen proteoglykaani ja yksi harvoista evoluutiossa konservoituneista kollageeneista. Se esiintyy elimistössä kolmena isomuotona, joiden biologiset tehtävät ovat vielä jokseenkin epäselviä. Tässä tutkimuksessa selvitettiin kollageeni XVIII:n isomuotojen fysiologista merkitystä hyödyntäen uusia hiirilinjoja, joilta kollageeni XVIII:n lyhyt tai kaksi pisintä varianttia oli geneettisesti inaktivoitu. Poistogeenisten hiirimallien rinnalle tehtiin kaikille varianteille yhteistä trombospondiini-1 (Tsp-1)-domeinia yli-ilmentävä hiirilinja. Tämän väitöskirjatutkimuksen avulla saatiin uutta tietoa kollageeni XVIII:n ja etenkin sen lyhimmän variantin tärkeästä roolista silmässä. Aikaisemmat tutkimukset ovat osoittaneet kollageeni XVIII:n puutteen häiritsevän silmän verkkokalvon verisuonituksen normaalia kehittymistä. Tässä työssä havaittiin, että pelkästään lyhyen isomuodon puute riitti altistamaan hiiret muutoksille verkkokalvon suonituksessa. Tsp-1-osan ylimäärän havaittiin lisäksi alistavan hiiret muutoksille silmän rakenteessa, mahdollisesti häiritsemällä silmässä jo olemassa olevan kollageeni XVIII:n toimintaa. Tässä työssä havaittiin myös uusi yhteys kollageeni XVIII:n ja rasvasolujen kypsymisen välillä. Verrokkihiiriin verrattuna muodostuvan rasvakudoksen havaittiin jäävän merkittävästi vähäisemmäksi poistogeenisillä hiirillä, joilta kollageeni XVIII:n pitkät isomuodot olivat geneettisesti inaktivoitu. Heikentynyt rasvakudoksen muodostuminen lisäsi triglyseridien kertymistä hiiren verenkiertoon ja maksaan. Tutkimustulos on merkittävä avaus soluväliaineen merkityksestä rasva-aineenvaihdunnalle ja kannustaa lisätutkimuksilla selvittämään, onko kollageeni XVIII:lla yhteys myös ihmisen metaboliseen oireyhtymään. Soluväliaineen komponenttien entsymaattinen muokkaus tuottaa usein molekyylejä, joilla on uusia isäntämolekyyleistä poikkeavia ominaisuuksia. Tässä työssä tutkittiin yhden tällaisen molekyylin, tyvikalvokollageenin IV hajoamistuotteen, arrestenin, suoria vaikutuksia syöpäsoluille. Arrestenin tiedettiin entuudestaan estävän syöpäkasvainten verisuonten uudismuodostusta koe-eläimillä. Työssä osoitettiin, että arresten vaikutti endoteelisolujen lisäksi myös itse syöpäsoluihin estäen niiden lisääntymistä ja vähentäen niiden elinkykyä ja liikkuvuutta, mikä tekee arrestenista entistä houkuttelevamman ehdokasmolekyylin lääkekehitystyöhön
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Béjar, Serrano María Teresa. „Impacto de los factores de riesgo cardiovascular en las células madre de tejido adiposo“. Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/400210.
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Las enfermedades cardiovasculares se desarrollan como consecuencia de la interacción entre factores genéticos y ambientales. Los factores de riesgo cardiovascular son una serie de condiciones que favorecen la aparición de eventos cardiovasculares, e incluyen la obesidad, la diabetes, la dislipemia y la edad entre otros. En los últimos años, la investigación de los mecanismos responsables del desarrollo de enfermedad cardiovascular ha tenido como importante objeto de estudio el tejido adiposo, ya que además de jugar un papel crucial en la regulación de la homeostasis energética, ha demostrado actuar como un potente órgano endocrino, y ser una fuente de células madre mesenquimales adultas (ASC). Se trata de células multipotentes, de fácil obtención, con propiedades inmunomoduladoras y con la capacidad de diferenciarse a múltiples linajes celulares. Por estas características, las ASC se consideran un candidato ideal para su uso en terapia celular y son objeto de numerosos estudios en medicina regenerativa. Sin embargo, es poco conocido el papel que juegan las ASC en el desarrollo de la patología cardiovascular, y el impacto que los factores de riesgo tienen sobre su funcionalidad.
En esta tesis hemos analizado las propiedades fenotípicas y funcionales de las ASC de distintas localizaciones adiposas en un modelo animal con acumulación de factores de riesgo. Hemos detectado diferencias intrínsecas de las ASC residentes en los distintos depósitos de grasa, relacionadas con su potencial de diferenciación, que se ven incrementadas en una situación patológica. Estas diferencias en las ASC ayudan a explicar la menor capacidad de expansión del tejido adiposo visceral y su consecuente mayor riesgo metabólico. Por otro lado, hemos demostrado que la presencia de factores de riesgo cardiovascular tiene un impacto negativo en las propiedades angiogénicas de las ASC subcutáneas y epicárdicas. Esta disminución de la capacidad para estimular la formación de vasos limita el uso autólogo de estas células para tratar enfermedades de carácter isquémico, pero también podría ser una de las causas de los problemas vasculares asociados a importantes factores de riesgo cardiovascular. Hemos identificado la vía de señalización Notch, en todos los casos, como un mecanismo clave en la regulación del potencial de diferenciación de las ASC, mediante el cual las modificaciones patológicas producidas por la acumulación de factores de riesgo cardiovascular tienen un impacto sobre la funcionalidad de las ASC de las distintas localizaciones adiposas. Adicionalmente, hemos observado que la médula ósea de donantes con factores de riesgo cardiovascular incrementa el fenotipo pro-aterogénico en receptores sanos, lo que podría explicar el elevado riesgo cardiovascular de pacientes sometidos a este procedimiento. Finalmente, en esta tesis se han descrito por primera vez las características fenotípicas y funcionales de las ASC derivadas de tejido adiposo perivascular coronario humano. Se ha observado una comunicación activa entre las ASC y las células musculares lisas, en un proceso mediado por la expresión de Tissue factor (TF) en las ASC. Este hallazgo, junto con la observación de altos niveles de expresión de TF en las ASC de pacientes con una elevada acumulación de factores de riesgo cardiovascular, abre un nuevo enfoque en la investigación sobre los procesos angiogénicos que se desarrollan en torno a la placa aterosclerótica en las arterias coronarias. Por tanto, los resultados de esta tesis demuestran que los factores de riesgo cardiovascular regulan las propiedades funcionales de las ASC de distintas localizaciones adiposas, y que dicho efecto está mediado en parte por la alteración de la vía de señalización
Notch. El efecto de los factores de riesgo cardiovascular sobre las ASC reduce el potencial de las mismas para la reparación espontánea de tejidos dañados y para su posible uso en terapia celular autóloga.Cardiovascular diseases are the leading cause of morbidity and mortality. Clustering of cardiovascular risk factors (CVRF), including diabetes, obesity and dyslipidemia among others, induces a chronic metabolic disturbance with implications in diverse cells and organ function. Adipose tissue is considered a dynamic endocrine organ playing a central role in homeostasis. Moreover, it is a source of adult multipotent stem cells known as adipose-derived stem cells (ASC). Due to their properties, ASC are potential candidates in regenerative medicine. However, the role of ASC in cardiovascular disease development and the impact of CVRF on their functionality is poorly understood. In this study, we analyzed the phenotype and function of ASC from an animal model clustering CVRF. Intrinsic differences related to differentiation potential were found in ASC from different fat depots, which were increased in presence of CVRF. These differences could contribute to the reduced expansion capacity of the visceral adipose tissue and its associated cardiometabolic risk. The presence of CVRF had a negative impact on the angiogenic properties of subcutaneous and epicardial ASC. A reduced ability to stimulate vessel formation limits autologous cell therapy in diabetic and obese patients, but could also be involved in the vascular problems associated to CVRF. We described Notch signaling pathway as a key regulator of the differentiation potential of ASCs from the different fat depots, and its activation was found altered by CVRF. Additionally, our results showed that the bone marrow from donors with CVRF increased the pro-atherogenic phenotype in healthy recipients, which could explain the high cardiovascular risk of patients undergoing bone marrow transplant. Finally, we characterized for the first time the ASC derived from human coronary perivascular adipose tissue. We described a novel cross-talk between ASC and vascular smooth muscle cells involving angiogenic and proliferative processes, regulated by a mechanism in part mediated by TF expression in ASC. Therefore, the results of this study demonstrate a significant impact of the presence of CVRF in the functional properties of ASC from different adipose depots, and provide evidence of a potential role of these cells in modulating angiogenic processes during cardiovascular disease development.
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Alexander, Lindsey Ann. „The Role of Inflammation in Diet-Induced Insulin Resistance“. University of Toledo / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1260808416.
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López, Fernández Daniel. „Efectos del trasplante de células madre en un modelo experimental de Fibrosis Pulmonar“. Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/572066.
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INTRODUCCIÓN: la Fibrosis Pulmonar Idiopatica (FPI) es una enfermedad intersticial de mal pronostico y una indicación de trasplante pulmonar. Actualmente, no existe un tratamiento medico curativo o capaz de cambiar el curso evolutivo de esta enfermedad. Las células madres (SC) presentan propiedades regenerativas e inmunomoduladoras y podrían ser una opción de tratamiento.
OBJETIVO: evaluar las propiedades protectoras de las SC derivadas de tejido adipose (ADSC) en un modelo experimental de Fibrosis Pulmonar (FP) inducida con bleomicina (BLM).
MÉTODO: Se analizaron 58 pulmones de 29 ratas macho Sprague-Dawley. Los animales se dividieron al azar en 5 grupos: a) Control (n=3); b) Sham (n=6); c) BLM (n=6); d) BLM+ADSC- 2d (n=6); e) BLM+ADSC-14d (n=8). La BLM se administró por via traqueal: 2,5UI/kg en 500μl de suero fisiológico (SF). Los animales Sham recibieron 500μl de SF por via traqueal.
Las ADSC (2x106 células en 100 ul de SF) se administraron por via traqueal a los 2 y 14 días después de la BLM. Los animales fueron sacrificados a los 28 dias. Se utilizó el índice de Ashcroft para determinar el grado de FP. Se determinó la expresión de Hsp27, Vegf, Nfkb, IL6, IL1, Col4 y Tgfβ1 mediante RT-PCR.
RESULTADOS: No hubo ningún caso de mortalidad. Los pulmones de los animales de control y sham mostraron una apariencia pulmonar normal. La Escala de Ashcroft fue: control=0; sham=0,37 }0,07; BLM=6,55 }0,34 vs sham (p=0,006). BLM vs BLM+ADSC-2d=4,63 }0,38 (p=0,005) y BLM+ADSC-14d=3,77 }0,46 (p=0,005). BLM vs sham incrementó significativamente la expresión de Hsp27 (p=0,018), Nfkβ (p=0,009),Col4 (p=0,004), Tgfβ1 (p=0,006) y disminuyó IL1 (p=0,006). BLM+ADSC-2d vs BLM disminuyó significativamente la expresión de Hsp27 (p=0,009) e incremento Vegf (p=0,006) y Nfkβ (p=0,009). BLM+ADSC-14d vs BLM disminuyó significativamente Hsp27 (p=0,028), IL6 (p=0,013) y Col4 (p=0,002), e incremento Nfkβ (p=0,040) y Tgfβ1 (p=0,002).
CONCLUSIONES: El trasplante trastraqueal de ADSC, no utilizado previamente, ha disminuido de forma significativa el grado de FP cuando el trasplante se ha realizado en fases precoces de la enfermedad (2 días) o en fases de enfermedad instaurada (14 dias). La administración trastraqueal permitió la utilización de dosis más bajas de ADSC que la vía intravenosa.
La expresión de Hsp27, Vegf, Nfkb, IL6, Col4, Tgfβ1 podría ser útil para monitorizar la respuesta al trasplante de ADSC en FP. Desde el punto de vista traslacional el trasplante de ADSC por vía traqueal podría ser una nueva opción de tratamiento de los pacientes con FPI.Idiopathic Pulmonary Fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis. Adipose stem cells (ADSC) have demonstrated regenerative properties in several tissues. The hypothesis of this study was that airway transplantation of ADSC could protect against BLM-induced Pulmonary Fibrosis (PF). METHOD: Fifty-eight lungs from 29 male Sprague-Dawley rats were analyzed. Animals were randomly divided into 5 groups: a) control (n=3); b) sham (n=6); c) bleomycin (BLM) (n=6); d) BLM+ADSC-2d (n=6); and e) BLM+ADSC-14d (n=8). Animals received 500μl saline (sham), 2,5UI/kg BLM in 500μl saline (BLM) and 2 x 106 ADSC in 100µl saline intratracheally at 2 (BLM+ADSC-2d) and 14 days (BLM+ADSC-14d) after BLM. Animals were sacrificed at 28 days. Blinded Ashcroft score was used to determine pulmonary fibrosis extent on histology. Hsp27, Vegf, Nfkβ, IL1, IL6, Col4, and Tgfβ1 mRNA gene expression were determined using qRT-PCR. RESULTS: Ashcroft index was: control=0; sham=0.37±0.07; BLM=6.55±0.34 vs sham (p=0.006). BLM vs BLM+ADSC-2d=4.63±0.38 (p=0.005) and BLM+ADSC- 14d=3.77±0.46 (p=0.005). BLM vs Sham significantly increased Hsp27 (p=0.018), Nfkβ (p=0.009), Col4 (p=0.004), Tgfβ1 (p=0.006) and decreased IL1 (p=0.006). BLM+ADSC- 2d vs BLM significantly decreased Hsp27 (p=0.009) and increased Vegf (p=0.006), Nfkβ (p=0.009). BLM+ADSC-14d vs BLM significantly decreased Hsp27 (p=0.028), IL6 (p=0.013), Col4 (p=0.002), and increased Nfkβ (p=0.040) and Tgfβ1 (p=0.002). CONCLUSIONS: Airway transplantation of ADSC significantly decreased the fibrosis rate in both early and established pulmonary fibrosis, modulating the expression of Hsp27, Vegfa, Nfkβ, IL6, Col4, and Tgfβ1. From a translational perspective, this technique could become a new adjuvant treatment for patients with IPF.
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Oñate, Hospital Blanca. „Caracterización transcriptómica y funcional de las células madre mesenquimales residentes en tejido adiposo de pacientes obesos“. Doctoral thesis, Universitat de Barcelona, 2013. http://hdl.handle.net/10803/132671.
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La obesidad se asocia con un estado de inflamación crónica de bajo grado y es considerada uno de los mayores factores de riesgo cardiovascular y de otro tipo de enfermedades como son la diabetes, hipertensión, arteriosclerosis y trombosis. Se han descrito diversos procesos que tienen lugar en el tejido adiposo y que determinan el desarrollo de la obesidad. Sin embargo, el tejido adiposo no solo se considera un órgano de almacenamiento energético o endocrino, sino que hoy en día también es considerado como una fuente de células madre mesenquimales (ASC). Recientemente las ASC se han convertido en una alternativa de gran interés en terapia celular para regenerar el corazón dañado. Sin embargo se ha sugerido que una alteración en la homeostasis de las células madre desencadenada por un estímulo nocivo, constante y repetitivo, como podría ser el caso de una enfermedad crónica, podría provocar un desequilibrio persistente en el reservorio de éstas células produciendo un cambio prematuro e irreversible del potencial regenerador de las células madre. De hecho, estudios previos han demostrado que la presencia de factores de riesgo cardiovascular, como la hipertensión, la enfermedad coronaria o la diabetes, alteran y merman las propiedades de las células progenitoras circulantes. Del mismo modo, se ha visto que la edad y el género modifican la funcionalidad de las ASC. El objetivo central de esta tesis ha sido el estudiar y caracterizar las ASC derivadas de pacientes obesos. En esta tesis doctoral se ha observado que la presencia de desórdenes metabólicos disminuye el porcentaje de células positivas para ciertos marcadores característicos de ASC, como es el caso de CD90, en el tejido adiposo. Sin embargo, una vez aisladas las ASC, independientemente del índice de masa corporal del donante de las ASC, éstas presentan el 100% de los marcadores característicos confirmándonos la obtención de una población homogénea. No obstante, hemos observado que algunas características importantes y necesarias para el uso de las ASC en la terapia celular se ven afectadas cuando las células se aíslan de pacientes que presentan obesidad mórbida y factores de riesgo cardiovascular. A nivel clínico y en la terapia celular es beneficioso poder obtener el máximo número de células en el menor tiempo posible. El hecho de que observemos una mejora en la velocidad de crecimiento celular al cultivar las ASC en condiciones de hipoxia refuerza el uso de bajas concentraciones de oxígeno a la hora de su expansión para fines clínicos. Sin embargo, el uso de las ASC de pacientes obesos no parece ser tan beneficioso. Estas células presentan un crecimiento celular más lento, una menor capacidad proangiogénica al liberar el factor antiangiogénico trombospondina-1, así como una capacidad de diferenciación disminuida respecto a las ASC de pacientes no-obesos. De hecho, parece ser que las ASC de pacientes obesos se encuentran en un estado de desarrollo menos multipotencial que las de individuos no-obesos, más dirigido hacia la adipogénesis, y a un estado más proinflamatorio. Una de las ventajas del uso de las ASC en la terapia celular es su uso autólogo, sin embargo esta ventaja desaparece en el caso de los pacientes obesos. Aunque se conocen bastante bien los cambios que se producen en el tejido adiposo de los obesos, no está muy estudiado como afectan estos cambios a la población endógena de células madre mesenquimales de éste tejido. Los resultados obtenidos en este trabajo nos ayudan a comprender mejor como la obesidad, y los desórdenes metabólicos que derivan de ella, afectan y modifican a la población de ASC.The adipose tissue is an endocrine regulator and a risk factor for atherosclerosis and cardiovascular disease when by excessive accumulation induces obesity. Moreover, it has been demonstrated that the adipose tissue is a reservoir of mesenchymal stem cells. The potential use of adipose-derived stem cells (ASCs) from white adipose tissue for organ repair and regeneration has been considered because of their obvious benefits in terms of accessibility and quantity of available sample. However, age, adipose tissue depot site, and gender have been shown to modify the number and the proliferation, differentiation, and angiogenic capacity of ASCs. Our aim was to investigate the mechanisms by which obesity affects subcutaneous white adipose tissue stem cells. Here we report that ASCs from white adipose tissue of patients with obesity have lower proliferative and angiogenic potential than ASCs of nonobese metabolically normal individuals. Moreover, the transcriptomic profile of the stem cells reservoir in obese subcutaneous adipose tissue is highly modified with significant changes in genes regulating stemcellness, lineage commitment and inflammation. In addition to body mass index, cardiovascular risk factor clustering further affect the ASC transcriptomic profile inducing loss of multipotency and, hence, capacity for tissue repair. In summary, obesity produces a detrimental effect on its resident stem cells. In fact, the ASC undifferentiated multipotent state is impaired in obese patients with respect to non-obese individuals. These effects may negatively influence their regenerative potential when used in cell therapy and also in spontaneous repair of minor organ damage. Indeed, ASCs have already been tested in several clinical trials, from repair of heart ischemic injury to Crohn’s disease and multiple sclerosis. However, our observations indicate that the therapeutic strategies based on autologous ASC implantation would be impaired in patients with obesity and metabolic syndrome.
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Suryawan, Agus. „Positive and negative regulators of adipocyte differentiation in primary culture“. Thesis, 1995. http://hdl.handle.net/1957/34624.
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Ortiz-Colón, Guillermo. „Investigation of adipogenic differences between bovine intramuscular and subcutaneous preadipocyctes“. Diss., 2006.
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Lee, Yu-Chun, und 李雨駿. „A Hybrid-Membrane Migration Method to Isolate Adipose-Derived Stem Cells from Fat Tissues Through Membranes Coated with Extracellular Matrices“. Thesis, 2019. http://ndltd.ncl.edu.tw/handle/5m95dy.
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碩士國立中央大學
化學工程與材料工程學系
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Human adipose-derived stem cells, hADSCs, can be obtained by isolation from fat tissue, which is currently a more practical source of stem cells than human induced pluripotent stem cells (hiPSCs) and embryonic stem cells (hESCs). Currently, several clinical trials use hADSCs, whereas only a few clinical trials have been performed using hiPSCs and hESCs. However, hADSCs are known to show heterogeneous characteristics and contain different pluripotency and differentiation abilities. Therefore, it is expected that the stem cell characteristics, pluripotency, and differentiation abilities should be different for hADSCs isolated by different isolation methods. hADSCs are typically isolated by cell culture of stromal vascular fraction (SVF, primary hADSC solution) where the SVF solution can be obtained by collagenase digestion of fat tissues followed by centrifugation. The isolated hADSCs can possess different purity levels and divergent properties depending on the purification methods used. It is innovated that the membrane migration method through Nylon mesh filter purifies hADSCs from a fat tissue solution with extremely high purity and pluripotency in my laboratory. A primary fat-tissue solution was permeated through the porous membranes (e.g., Nylon mesh) with a pore size from 8 to 25 μm, and the membranes were incubated in cell culture medium for 15-18 days. In this study, I developrd a new membrane migration method using Nylon mesh membranes having optimal pore sizes, 11 and 20 μm, and PLGA/silk membranes where optimal extracellular matrix (ECM) was coated on the membranes, which could purify hADSCs. The isolated hADSCs are expected to have high pluripotency and high differentiation ability into chondrocytes, osteoblasts and adipocytes. hADSCs were isolated from adipose tissue by the membrane migration method where different membranes were used, e.g., (a) Nylon mesh and PLGA (poly (lactic-co-glycolic acid))/silk screen membrane, (b) Nylon mesh and PLGA/silk screen membrane coated with collagen type I, (c) Nylon mesh and PLGA/silk screen membrane coated with human recombinant-vitronectin, (d) Nylon mesh and PLGA/silk screen membrane coated with human fibronectin. Collagen type I is xeno-containing materials, whereas another extracellular matrices (ECMs) were xeno-free materials. The hADSCs that migrated from the membranes kept an extremely high percentage (e.g., >98%) expression of mesenchymal stem cell markers (CD44, CD73, and CD90) and showed almost one order of magnitude higher expression of some pluripotency genes (Oct4, Sox2, and Nanog) compared with cells isolated using the conventional culture method.