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1
Wilson, Robin A. "Investigating molecular adaptations in adipose tissue and skeletal muscle in response to intermittent fasting and exercise training." Thesis, 2018. https://vuir.vu.edu.au/42888/.
Full textAbstract:
The rapid rise in obesity prevalence appears to be a reflection of the changes in dietary and behavioural patterns, with eating habits shifting to higher consumption of energy-dense foods which are rich in fats and sugars, while at the same time, levels of physical activity are decreasing. These differences in energy intake and expenditure, often referred to as energy balance, have direct implications for weight regulation, with even small deviations in daily energy balance resulting in large body weight changes over the long term. Diet and exercise interventions aiming to shift the energy balance towards negative by either decreasing caloric intake and/or increasing physical activity have shown to be effective for weight loss. Many iterations of such dietary and physical activity interventions have been proposed, but intermittent fasting (IF) and high intensity interval training (HIIT) have recently been purported as effective strategies. Despite their effectiveness, the molecular mechanisms by which these lifestyle interventions induce their effects are unclear. Therefore, the purpose of this thesis was to examine the effects of IF and HIIT, alone and in combination, on anthropometric and metabolic health parameters in a model of diet-induced obese mice. To elucidate possible mechanisms of action, we investigated the impact of both lifestyle interventions on mRNA-miRNA regulatory networks, but more importantly, how such changes may translate into exercise- induced and diet-induced improvements in body composition and metabolic health. The findings from the thesis demonstrate that intermittent fasting with or without high intensity interval training resulted in significantly less weight gain in male mice despite concurrently consuming a high fat and sugar diet. The reduced weight gain was predominantly in the form of lower fat mass accumulation, with no significant loss in lean mass. These observations were supported by enhanced expression of adipose tissue genes relating to fragmentation of unilocular lipid droplets, lipolysis, fatty acid oxidation and efflux. Moreover, lower expression levels of leptin, pro-inflammatory markers and markers of hypoxia were also observed. These changes were also reflected by changes in miRNA-24, -222, -145 and -143. Within the skeletal muscle, the combination of diet and exercise demonstrated minimal impact on mRNA and miRNA expression markers relating to energy metabolism, however IF alone displayed significantly lower expression of all markers compared to control mice or other intervention groups. Interestingly, the changes in body composition, glycaemic control, lipid panels and expression of mRNA and miRNA seem to be gender specific with different responses, independent of intervention, demonstrated in male mice compared to the female mice. In conclusion, the novel results from this thesis have demonstrated superior effects on body composition and lipid profiles following combined IF and HIIT compared to either diet or exercise intervention alone while concurrently consuming a high fat and sugar diet. These observations are likely due to the physiological and biochemical changes that occur within the adipose and skeletal muscle tissue when creating a negative energy balance shift. The gender specific responses to the same diet and/or exercise intervention could indicate potential hormonal differences influencing metabolic control/adaptation in mice. Identification of important regulatory miRNAs through this thesis could provide potential therapeutic targets for obesity treatment and management.
2
O'Connell, Brett. "A study of rat skeletal muscle Troponin C isoforms." Thesis, 2005. https://vuir.vu.edu.au/15657/.
Full textAbstract:
The investigations described in this thesis were prompted by an overall interest in the phenomenon of Troponin C (TnC) polymorphism in mammalian skeletal muscle. Gaining
insights into this area of inquiry has been limited, in large part due to methodological problems associated with the identification of rat (a commonly used animal model for
studying mammalian skeletal muscle) TnC isoforms on SDS gels. Therefore, a method was devised for unambiguous identification of TnC isoforms in rat single muscle fibres.
This method, validated using rat skeletal muscle TnC isoforms purified for the first time as part of this study, was used in conjunction with myosin heavy chain (MHC) isoform based fibre-typing and Sr2+ -activation measurements to explore the relationship between MHC and TnC isoform composition in mammalian skeletal muscle at the single fibre level, and to revisit the controversial issue of the relationship between TnC isoform composition and fibre-type differences with respect to Sr2+ -activation characteristics.
3
Horvath, Deanna Maree. "The effect of taurine on dystrophic muscle tissue function." Thesis, 2011. https://vuir.vu.edu.au/19424/.
Full textAbstract:
Duchenne muscular dystrophy (DMD) is a lethal X-linked genetic disorder which results in chronic degeneration of skeletal muscle, significantly impacting on the duration and quality of life. Despite the genetic defect and the missing protein dystrophin having been identified and characterised over 20 years ago, curative genetic therapies are still not clinically applicable, and corticosteroids, which are the only significantly beneficial treatment option currently available to DMD patients, are associated with several side-effects. Thus, there is a need for additional therapeutic interventions that can improve skeletal muscle function and delay the onset of severe pathology in dystrophy. The amino acid taurine is essential for normal skeletal muscle function, and has been shown to act on several factors thought to be key contributors to the development of skeletal muscle pathology in dystrophy. Moreover, as dystrophic skeletal muscle demonstrates a significant decrease in taurine content, it is possible that raising intramuscular taurine stores may preserve muscle function in dystrophy, and thus have potential therapeutic applications. Despite this, only two studies have ever examined the effect of taurine supplementation on dystrophic muscle function. The purpose of this thesis was to examine the effect of taurine on dystrophic skeletal muscle function, which was performed in three studies using the dystrophic mdx mouse as a model for DMD.
4
(8933363), Ahmad Abdurahman M. Alhulail. "FAT AND SODIUM QUANTIFICATION AND CORRELATION BY MRSI." Thesis, 2020.
Find full textAbstract:
Lipids and sodium (23Na) are two essential components of the human body. They play a role in almost all biological systems. However, an increase in their levels is associated with metabolic diseases. The elevation of their contents can cause similar health disorders. Examples of prevalent disorders that share an increase of musculoskeletal lipids and 23Na are hypertension and diabetes. However, the relationship between in vivo lipid and sodium levels in pathophysiology has not been studied enough and therefore is still unclear. Additionally, the available quantification methods to facilitate such a study may not be practical. They are either invasive, not sensitive enough, or require an impractical measurement time.
Therefore, in this work, our aims were to develop practical in vivo methods to quantify the absolute sodium concentration as well as the concentration of each lipid component individually, and to study the correlation between them within the skeletal muscles.
Since lipids and 23Na have different nuclear magnetic resonance properties, their quantification by magnetic resonance (MR) techniques face different challenges. Thus, we optimized different MR spectroscopic imaging (MRSI) techniques for lipids and 23Na.
Our proposed proton MRSI was able to provide eight lipid fat fraction (FF) maps representing each musculoskeletal lipid component (fatty acid) detected by our MRSI technique, and demonstrated a superior sensitivity compared to the conventional MR imaging methods.
For 23Na, our developed 23Na-MRSI was able to measure and map the absolute 23Na concentration with values agreeing with those reported previously in biopsy studies, and with a high repeatability (CV < 6 %) within significantly shorter acquisition time compared to other available techniques.
Finally, the 23Na concentration and the fat fractions of each lipid component within healthy skeletal muscles were measured and correlated using our developed MRSI methods. Our findings suggest a positive regional relationship between 23Na and lipids and negative correlation between 23Na and BMI under healthy conditions.
5
Williams, Andrew Dafydd. "Skeletal muscle structure and metabolism in chronic heart failure." Thesis, 2005. https://vuir.vu.edu.au/15730/.
Full textAbstract:
Chronic heart failure (CHF) patients have poor exercise tolerance, which does not correlate with impaired central function. Consequently factors other than impaired cardiac function must contribute to the exercise intolerance. Maladaptations in skeletal muscle appear to be a likely
reason for the limited exercise tolerance. In study I, exercise tolerance and skeletal muscle metabolism and morphology were examined in 17 CHF patients and eight healthy similarly aged sedentary control subjects. In Study II, thirteen CHF patients participated in a study on the effects of resistance training on exercise tolerance and skeletal muscle morphology and metabolism.
6
Cheung, Anne Lise Tang Fook. "Assessing calcium absorption from fortified soymilk and fermented fortified soymilk in osteopenic post menopausal women." Thesis, 2010. https://vuir.vu.edu.au/19399/.
Full textAbstract:
The overall objectives of this thesis were to assess the calcium absorption of
calcium fortified soymilk (CFSM) compared to cows’ milk in post menopausal women,
and to investigate ways of optimising the calcium bioavailability from commercially
available CFSM. The project consisted of two parts: in vitro studies and the in vivo
clinical studies.
7
O'Keefe, Lannie. "Determining the Influence of Endocannabinoids in Skeletal Muscle Adiponectin sensitivity in Diet Induced Obesity and Diabetes." Thesis, 2017. https://vuir.vu.edu.au/41735/.
Full textAbstract:
Obesity kills more than 2.8 million people globally each year regardless of economic status or
age. The endocannabinoid system is a widely distributed lipid signalling system that regulates
appetite, fatty acid oxidation, glucose metabolism and inflammation. Adiponectin plays a
protective role against metabolic disorders. Skeletal muscle plays a leading role in fatty acid
oxidation and glucose metabolism. Activation of Cannabinoids in adipose tissue results in a
decrease in adiponectin and an increase in inflammation causing ER stress. Blocking
cannabinoids causes a decrease in inflammation and increase in adiponectin. This suggests a
direct yet to be determined relationship between the Endocannabinoid system and adiponectin
resistance, which was the focus of this candidature.
Sprague Dawley rats were fed a HFD (22%) for 12 weeks to elicit DIO, then injected daily (IP)
with CB1 Antagonist (AM251- 3mg/kg) for 6 wks. Animals were anesthetised, and skeletal
muscles (Red /White fibre types) surgically removed. Skeletal muscle was immediately placed
in organ bath (37C
-95%O25%) with Adiponectin for 30 minutes. Plasma analysis determined
that chronic CB1 Antagonism in these rats resulted in a significant reduction in food intake,
weight reduction, a reduction in Peri-renal and brown adipose tissue weight, and a reduction in
plasma leptin and Glucagon. There was an increase in inflammatory plasma cytokines (Il-1α,
IL-2, Il-4, Il-5, Il-17α, Il-18, RANTES, IL12p70). Muscle analysis found that CB1 Antagonism
on whole muscle resulted in no changes in mitochondrial markers. Incubation of the soleus
muscle with adiponectin showed a significant decrease in AdipoR1 expression. There was a
decrease in markers of fatty acid oxidation in white skeletal muscle
Sprague Dawley rats were fed HFD (22%) for 12 weeks then injected daily (IP) with either
CB2 Agonist (AM1241-3mg/kg or CB2 Antagonist (AM630- 0.3mg/kg) for 6 wks. Animals
were anesthetised, and muscles (Red and White fibre types) were surgically removed. Muscle
was placed in an organ bath (37C
-95%O2-5%) with Adiponectin for 30 minutes. Plasma
analysis determined that CB2 modulation resulted in an initial decrease in food intake. CB2
stimulation caused an increase in IL12p70 and a decrease in Leptin in plasma. CB2 Antagonism
caused a decrease in plasma Leptin, GLP-1, Ghrelin. Muscle analysis showed that blocking
CB2 caused an increase in mitochondrial activity in red fibres via elevated concentrations of
citrate synthase. Adiponectin exposure resulted in CB2 agonism causing a down regulation of
the mRNA expression of both AMPK and PGC1α in the Extensor Digitorum Longus muscle.
Human skeletal muscle (rectus abdominus) were sourced from Obese and Diabetic individuals
undergoing routine lap band surgery. Myotubes were treated for a 24-hour period with either
CB1 antagonist (AM251), CB2 antagonist (AM630) in isolation or in combination with
Adiponectin. Results showed significant increase of AdipoR2 in combination with Adiponectin
in Diabetic tissue. Blocking CB2 caused an increase in both AdipoR1 and AdipoR2 expression
in diabetic tissue.
The results of this thesis are the first to support the hypothesis of synergistic mechanisms at
play between Endocannabinoids and Adiponectin in the skeletal muscle of Obese and Diabetic
skeletal muscle tissue.
8
Metcalfe, Stephen R. "The physiological characteristics of elite women's basketball." Thesis, 1998. https://vuir.vu.edu.au/17881/.
Full textAbstract:
Increasing numbers of Australians are playing the sport of basketball. The
game's ability to be played both indoors and outdoors, and the international
popularity of the game make it an appealing sport for people of all ages. With
an impressive 198 countries affiliated with the International Basketball
Federation and an incredible 100,000,000 (one hundred million) women throughout the world playing basketball, the position of women's basketball has
never looked stronger. According to Basketball Australia, females constitute
50% of the registered basketball playing population in Australia with
approximately 350,000 participants. Participation rates have doubled in the last
seven years.
One of the factors believed to have contributed to the growth in the number of
women playing basketball in Australia, is the increased profile of the Women's
National Basketball League (WNBL). According to Leanne Grantham, Chief
Executive of the WNBL, record crowds were recorded throughout the 1995/96
seasons with a subsequent rise in the level of media interest. The WNBL was
one of Australia's first full home and away sporting competitions for women and
is considered to be one of the three most competitive female basketball
competitions in the world. This is reflected in the high number of overseas
players (imports) who seek to join the competition each year.
Tom Maher, Head Coach of the Australian Senior Women's Basketball Team
(Opals), advocates that the standard of the WNBL is in a large way responsible
for the success of Australian Junior and Senior Teams at international
competitions. The Australian Junior Women's Team (Gems) won a silver medal
at the 1997 World Junior Championships and is currently ranked two in the
World and the Senior Women's Team, which won its first ever Olympic medal
(bronze) at the 1996 Atlanta Olympic Games, is currently ranked three.
Given the increase in the profile of women's basketball both in Australia and
overseas, it is interesting to note the limited number of studies which have
investigated the physiological requirements of the game. A physiological
investigation of elite women's basketball may provide answers to questions such
as: What is the nature of the physiological strain incurred by elite players during
performance? Which system does the majority of energy contribution during
performance come from? What type of specific strength and conditioning is
required? Do the physiological stresses placed on elite women basketballers
vary according to position?
9
Lees, Catherine. "Cancer immunotherapy with Mucin-1 and cytokines." Thesis, 2000. https://vuir.vu.edu.au/15628/.
Full textAbstract:
Cancer immunotherapy involves the manipulation of the immune response to combat tumour cells. The studies contained within investigated the role of cytokines in the anti-tumour immune response to the cancer antigen, MUCl, which is over produced in an altered form in cancers of the breast, pancreas, and ovary making an ideal target for immunotherapy. MUCl coupled to oxidised mannan (MFP), forms a powerful immunotherapeutic reagent capable of inducing tumour regression and cell mediated immune responses that protect against tumour challenge in many in vivo tumour models. This thesis characterised the Tl cytokine profile
induced from CD8+ and CD4+ T cells following immunisation with MFP and suggested a role for IL-12 in the MUCl anti-tumour immune response. The addition of various combinations
of Tl and T2 cytokines to MFP injections considerably increased the MUCl CTLp response, and demonstrated a role for IL-5 in the induction of cytotoxic T cells. A MUCl mammary carcinoma tumour was characterised to provide a more realistic model for MUCl immunotherapy studies. However, of particular significance was the discovery that additional IL-12 included in MFP immunisations,considerably decreases tumour growth in MUCl transgenic mice and significantly increases the MUCl specific CTLp response. The use of IL-12 and MFP in cancer immunotherapy has now progressed into Phase I human clinical trials in cancer patients.
10
McInnes, Simon E. "The physiological load imposed on basketball players during game play." Thesis, 1993. https://vuir.vu.edu.au/15765/.
Full textAbstract:
The purpose of this study was to investigate the intensities of work and the patterns of play during men's basketball and, in addition, to investigate the exercise metabolism that meets the energy demands of participation. Eight (8) male basketball players participating in the
1992 National Basketball League (NBL) were monitored during practice games and Victorian Basketball Association games. Each subject was videoed during competition and had his HR monitored at 15 second intervals throughout the game. In addition, arterialised blood samples were obtained at various stages throughout the game and analysed for lactate
concentration.
11
Cheethirala, Maharshi Bhaswant. "Investigation of phytonutrients in the treatment of cardio-metabolic disease." Thesis, 2016. https://vuir.vu.edu.au/31824/.
Full textAbstract:
This thesis investigated the effect of different foods such as spices (green cardamom and black cardamom), vegetables (beetroot), cereal grains (purple maize), fruits (chokeberry and Queen Garnet plum) and bioactive molecules (sodium nitrate and cyanidin 3-glucoside) on risk factors for metabolic syndrome using a diet-induced obese rat model. Obesity, insulin resistance, impaired glucose tolerance, atherogenic dyslipidaemia, hypertension and endothelial dysfunction are the major components of metabolic syndrome. Maintaining a healthy lifestyle including regular exercise together with a healthy and balanced diet has been recommended as the first-line of defence to prevent metabolic syndrome. However, with the growing prevalence of obesity worldwide, this complex disorder is considered to be a clinical challenge and an important public health concern. While current pharmaceutical drug therapies for obesity show some benefits, there are also multiple side effects. Hence, complementary and alternative therapies have become popular to reduce the incidence of metabolic syndrome with the aim of decreasing future health risks.
12
Danaher, Jessica. "Metabolic mechanisms of the fat mass and obesity-associated (FTO) gene." Thesis, 2016. https://vuir.vu.edu.au/34710/.
Full textAbstract:
The modern obesogenic lifestyle encompasses an environment that promotes weight
gain in the form of body fat accumulation. Genetic variations can predispose some
individuals to be more susceptible to developing obesity in a similar environment
(Hainer et al. 2000; Maes et al. 1997; Mustelin et al. 2009). As the prevalence of
obesity increases worldwide, and becomes a substantial socioeconomic issue, the need
for research that deepens our understanding of the underlying genetic influences on
complex regulatory mechanisms governing energy homeostasis becomes increasingly
necessary. The fat mass and obesity-associated (FTO) gene has been strongly linked
to an increased obesity risk through numerous genome wide association (GWA)
studies over the past decade. However, information regarding FTO’s peripheral
influences, specifically on skeletal muscle metabolism, is limited. The broad aim of
this dissertation was to identify metabolic differences between risk allele and non-risk
variants of FTO, and to determine the impact of physical stress (in the form of
exercise) on FTO expression and function. Thus, the experiments presented in this
dissertation were designed to investigate whether differences across genotype alleles
of the FTO rs9939609 (T>A) polymorphism existed for metabolic flexibility in
response to a nutritional challenge, and for metabolic profiles, FTO expression and
FTO function in skeletal muscle following acute exercise stimuli.
13
Smith, Renee Melissa. "The Role Of Putative Nox Inhibitors In Homocysteine-Induced Vascular Dysfunction." Thesis, 2018. https://vuir.vu.edu.au/39496/.
Full textAbstract:
Excess plasma homocysteine (Hcy; hyperhomocysteinemia, HHcy) remains an independent risk factor for cardiovascular disease (CVD) and treatments remain elusive. The source of Hcy, methionine, is an essential amino acid acquired by ingestion of animal foods. Normal methionine metabolism effectively removes Hcy via recycling back into methionine or excretion via the kidney. However, in aberrant methionine metabolism, Hcy accumulates and causes damage to the vascular system by increasing oxidative stress; the exact mechanism of how this occurs is unknown. Importantly, the B vitamins B6, B9 and B12 are essential to proper methionine/Hcy metabolism and are often found in low levels in patients presenting with HHcy; this has provided a potentially viable treatment strategy in the clinical setting. Disappointingly, clinical trials administering B vitamins to reduce HHcy have been unsuccessful in reducing CVD and treatments continue to be sought.
The NADPH oxidase (Nox) family of enzymes are expressed in a broad range of cell types throughout the body and are the primary source of superoxide (Nox1, Nox2) and hydrogen peroxide (Nox4) within the vasculature under both physiological and pathological conditions. Nox1, 2 and 4 are of primary interest in vascular disease, as there is evidence that Hcy can interfere with the proper function of Nox1, 2 and 4 signalling, potentially leading to an over-expression of pro-oxidants. Nox1, 2 and 4 have been implicated in vascular disease (endothelial dysfunction), hypertension, vascular inflammation, stroke, diabetes, and atherosclerosis, and putative inhibitors of these enzymes are now available. Additionally, nitric oxide (NO) is also measured as a marker of proper vascular function; indeed, the current gold standard of assessing NO availability is by indirectly measuring vascular responses to acetylcholine. Accordingly, a loss of NO bioavailability is linked to the development of many of the same vascular pathologies caused by HHcy and also potentially increased Nox1, 2, and 4 activity.
Thus, this thesis examined if current putative Nox inhibitors could prevent vascular dysfunction caused by homocysteine (as indirectly measured by acetylcholine-mediated vasorelaxation). Using New Zealand white rabbits, C57BL/6 mice and a Nox2-/- (C57BL/6 background) mouse models, we observed that pharmacological intervention with single Nox1, 2 and 4 inhibitors reduced the effect of acetylcholine on vasorelaxation. In 1% methionine-fed Nox2-/- mice, we observed an improvement in function. We also assessed combinations of Nox1, 2 and 4 inhibitors and found that, although function was not restored to control levels, it was improved compared with single Nox inhibition. Due to these results, we performed a gp91ds-tat dose response in rabbit aorta. We found that in our models of vascular dysfunction, lower doses of gp91ds-tat significantly improved acetylcholine-mediated vasorelaxation. These results showed for the first time that in both pharmacological and diet-induced HHcy, high dose putative Nox inhibitors might not be effective.
In conclusion, the observations made in this thesis highlight the important role that Hcy plays in the redox balance in the context of vascular function. Future work in this area should focus on low dose Nox inhibition in Hcy induced disease in in vivo models, in order to better determine which drug can be used to HHcy induced vascular damage.
14
Hong, Yet Hoi. "Regulation of skeletal muscle glucose uptake during contraction/ exercise by nitric oxide (NO)/ neuronal nitric oxide synthase MU (NOSμ)." Thesis, 2014. https://vuir.vu.edu.au/25848/.
Full textAbstract:
During exercise/ muscle contraction, large amounts of blood glucose are taken up into skeletal muscle fibers thus removing glucose from the bloodstream. This process is regulated differently to insulin-stimulated muscle glucose uptake and is normal in humans with type 2 diabetes (T2D) and in diabetic rodent models. A number of candidates have been implicated to play a role in the regulation of skeletal muscle glucose uptake during contraction and it is likely that there is some redundancy. In humans, there is convincing evidence that nitric oxide (NO) plays a role in contraction-stimulated muscle glucose uptake and may be promising from a therapeutic standpoint for people with T2D since they have a greater reliance on NO-mediated glucose uptake during exercise. However, evidence for a role of NO in regulating contraction-stimulated muscle glucose uptake in rodents is conflicting, most likely due to methodological inconsistencies. Studies have almost entirely involved the use of NO synthase (NOS) inhibitors with little data in genetically-modified models examining the role of NO in contraction-stimulated glucose uptake. Neuronal NOSμ is the major NOS isoform that activates the NO/ cGMP downstream signalling during skeletal muscle contraction. In this thesis, the role of NO/ nNOSμ in the regulation of skeletal muscle glucose uptake was examined. In rodents, NO/ nNOSμ is also involved in the regulation of skeletal muscle blood flow during contraction/ exercise, and glucose uptake is influenced by blood flow and glucose delivery. Therefore, mice lacking nNOSμ were used to investigate its role in glucose uptake during both ex vivo contraction and more physiological in vivo treadmill exercise. Also, a T2D rat model was generated and used to investigate if diabetic rats have a greater reliance on NO-mediated muscle glucose uptake during in situ contraction, as has previously been shown during exercise in people with T2D.
15
Gartlan, Kate Helen. "A complementary role for the tetraspanins CD37 and Tssc6 in the immune system." Thesis, 2008. https://vuir.vu.edu.au/29497/.
Full textAbstract:
The co-operative nature of tetraspanin-tetraspanin interactions in membrane organisation
suggests that functional overlap is likely to be a factor in tetraspanin biology. CD37 and Tssc6
are immune/haematopoietic restricted tetraspanins, whose function has been previously
investigated with CD37"7" and TSSC6"7" knockout mice. Both strains display hyper-proliferative T
cell responses to in vitro stimulation, suggesting that functional overlap may occur between
these two tetraspanin molecules in the immune system. To test this hypothesis, the
immunophenotype of a tetraspanin "double knockout' mouse (CDST^Tssce-7") is described.
16
Granata, Cesare. "Effects of different exercise intensity and volume on markers of mitochondrial biogenesis in human skeletal muscle." Thesis, 2015. https://vuir.vu.edu.au/30176/.
Full textAbstract:
Mitochondria are key components of skeletal muscles as they provide the energy required for almost all cellular activities, and play an important role in ageing and cell pathology. Different forms of exercise training have been associated with mitochondrial adaptations, such as increased mitochondrial content and function, and enhanced mitochondrial biogenesis, as well as improved endurance performance. However, the role of training intensity and training volume, in determining these changes remains elusive. Therefore, the aim of this thesis was to investigate the role of training intensity and volume on changes in mitochondrial content and function (as measured by mitochondrial respiration in permeabilised muscle fibres), in the skeletal muscle of healthy humans, and to study the molecular mechanisms underlying these changes. It was demonstrated that training intensity is a key factor regulating changes in mitochondrial respiration, but not mitochondrial content, and that an apparent dissociation exists between changes in these two parameters. Training consisting of repeated 30-s “all-out” sprints lead to improved mitochondrial (mt)-specific respiration (indicative of improved mitochondrial quality). Conversely, training volume was shown to be a key factor regulating mitochondrial content, with the associated increase in mitochondrial respiration being likely driven by the increase in mitochondrial content (i.e., unchanged mt-specific respiration). A training volume reduction resulted in a rapid decrease in most mitochondrial parameters, underlining the importance of maintaining the training stimulus to preserve training-induced mitochondrial adaptations. The protein content of PGC-1α, p53 and PHF20 was shown to be regulated in a training intensity-dependent manner, and was more strongly associated with changes in mitochondrial respiration rather than content, whereas changes in the protein content of TFAM were primarily associated with changes in mitochondrial content. Moreover, it was demonstrated that exercise intensity induced an increase in nuclear PGC-1α protein content and nuclear p53 phosphorylation, two events that may represent the initial phase of different pathways of the exercise-induced adaptive response. Collectively, this research provides novel information regarding mitochondrial adaptations to different training stimuli, and could have important implications for the design of exercise programs in conditions of compromised mitochondrial function.
17
Rai, Sudarshan. "Understanding the role of MasR in vascular pathology." Thesis, 2016. https://vuir.vu.edu.au/35026/.
Full textAbstract:
Homocysteine was first suggested as a risk to CVD in 1969. Since then, elevated
plasma homocysteine (derived from methionine) has remained a cardiovascular risk factor with no
current treatment. Homocysteine is known to stimulate NADPH oxidase, and NADPH oxidase can
be inhibited by stimulation of the Mas receptor (MasR) of the renin angiotensin system. Stimulation
of MasR is known to reduce organ fibrosis through the production of NO. However, the role that
MasR plays in homocysteine-induced vascular pathology, including endothelial dysfunction and
organ fibrosis, is not known. The aim of this thesis is to determine if high methionine diet in MasR-/- mice will worsen cardiovascular pathology.
18
Jenkin, Kayte. "Renal Cannabinoid Receptor Expression and Function: Their Role in Obesity and Diabetes." Thesis, 2014. https://vuir.vu.edu.au/25829/.
Full textAbstract:
Obesity and diabetes are clearly established independent risk factors for renal
disease. Therapeutic targets have been investigated for their role in treating obesity
and diabetic associated renal damage. The endocannabinoid system is an important
endogenous lipid signalling system known to mediate glucose and lipid metabolism,
inflammation and energy storage. Specifically, diabetes mellitus and obesity induces
alterations in the expression of cannabinoid receptor 1 (CB1), cannabinoid receptor
2 (CB2) and putative cannabinoid receptor G-protein coupled receptor 55 (GPR55)
in a tissue specific manner. Renal expression and function of these receptors,
particularly within the pathophysiological context of obesity and diabetes related
renal damage is poorly understood. The research presented in this thesis examines
the renal expression and function of CB1, CB2 and GPR55. The significant aim of
this PhD candidature was to examine the expression of cannabinoid receptors in the
kidney in obese and diabetic conditions. Subsequent studies sought to evaluate the
actions of selective manipulation of the receptors by synthetic compounds on
markers of renal damage and structure in an animal model of diet induced obesity
(DIO).
19
Hua, Bin. "Evaluation of the efficacy of a Chinese herbal medicine in the treatment of patients with osteoarthritis of the knee." Thesis, 2011. https://vuir.vu.edu.au/19407/.
Full textAbstract:
Osteoarthritis (OA) is common but has no outright cure. Current therapeutic drugs mainly treat OA symptoms and often cause undesirable side effects. Chinese medicine (CM) is a popular alternative therapy for OA, however the majority of CM efficacy studies have been methodologically inadequate. CM has traditionally treated OA under the clinical descriptor of ‘Bi Syndrome’ (painful obstruction syndrome) which includes a range of musculoskeletal disorders. An emerging theory treats OA as a combination of two types of CM Syndromes: Bi Syndrome and Wei Syndrome (atrophy syndrome). There is a lack of objective evidence with respect to possible CM Syndromes of OA, the reliability of CM diagnosis and efficacy of CM treatment guided by this emerging theory.
20
Sullivan-Gunn, Melanie. "An investigation of NADPH oxidase in normal and diseased skeletal muscle." Thesis, 2009. https://vuir.vu.edu.au/15838/.
Full textAbstract:
Oxidative stress has been implicated in various progressive degenerative conditions, such as skeletal muscle wasting and therefore this study sought to determine a role for the superoxide generating NADPH oxidase and antioxidant enzyme systems in conditions of skeletal muscle wasting. The results of these studies indicated changes in the gene expression of important components of NADPH oxidase in animal models of age-associated sarcopenia, cancer-induced cachexia and a model of antioxidant superoxide dismutase overexpression. Also observed were changes in superoxide dismutase that appeared to contribute significantly to alterations in cellular reactive oxygen species and contribute to skeletal muscle wasting in these conditions. While these oxidative and antioxidative systems demonstrated complex changes in these models, NADPH oxidase is indeed altered in response to aging, cancer and superoxide dismutase overexpression, which appear to be involved in complex redox-sensitive signaling that essentially regulates skeletal muscle atrophy and hypertrophy pathways.
21
Zurzolo, Giovanni. "The Role of Precautionary Labelling for Food Allergens and the Care of Children with Food Allergies." Thesis, 2014. https://vuir.vu.edu.au/25921/.
Full textAbstract:
There is no current cure for food allergy; therefore consumers with food allergy rely on accurate and detailed information on food labels in order to prevent an adverse reaction. Manufacturers cannot guarantee that food products are free from allergens as cross contamination can occur in several situations including but not limited to raw materials, the actual premises, storage and distribution, manufacturing processes and cleaning procedures. In order to alert the allergic consumer to the possible presence of trace allergens, manufacturers have voluntarily added precautionary labelling to processed foods. There are several variations to these statements, for example: “may contain traces of”, “may be present “and “made on the same production line”. The main purpose of this thesis is to understand the role of precautionary labelling in the care of children with food allergies.
22
Pompeani, Nancy. "The Effects of Dietary Supplements on Skeletal Muscle Function in Type 2 Diabetic Rats." Thesis, 2016. https://vuir.vu.edu.au/32315/.
Full textAbstract:
Type 2 Diabetes is considered to be a heterogeneous disease, and whilst its pathogenesis is currently unknown, it is often characterized by high plasma free fatty acids (FFAs), hyperglycaemia, and altered insulin secretion from pancreatic β-cells. Whilst multiple organ systems are often affected by the disease, the effects on skeletal muscle in particular are pertinent, as this is the main organ responsible for glucose disposal, and also has a major role in basal and altered metabolism. The overall aim of this thesis is to examine the extent of any changes to skeletal muscle morphology and (dys)function in Type 2 Diabetes and how these can be improved by the use of dietary supplements. Specifically, the potential of Creatine Monohydrate, Whey Protein Isolate, and Aspirin on the contractile apparatus and specific intramyocellular organelles will be tested in order to reverse some of the maladaptations found in skeletal muscle of Type 2 Diabetic patients.
23
Snow, Rodney J. "The effect of endurance training on human ammonia metabolism." Thesis, 1988. https://vuir.vu.edu.au/15694/.
Full textAbstract:
This thesis examines human ammonia (NH3)
metabolism in trained and untrained individuals.
Specifically, these aspects include: 1) plasma NH3
accumulation during exercise at similar absolute and
relative work intensities; 2) plasma NH3 accumulation
during recovery from maximal exercise; 3) the absolute and
relative work intensities at which blood lactate (LA) and
plasma NH3 concentrations begin to rapidly accumulate
(i.e the LA breakpoint - LABP, and NH3 breakpoint -
NH3BP); 4) the relationship between the NH3BP and LABP,
and 5) the relationship between plasma NH3, blood (LA),
and muscle fibre type.
24
Steward, Collene H. "Na+,K+-ATPase in human skeletal muscle: the effects of glucose and sodium bicarbonate, and determination of cellular localisation via immunofluorescence." Thesis, 2014. https://vuir.vu.edu.au/30179/.
Full textAbstract:
The sodium-potassium adenosine triphosphatase enzyme (Na+,K+-ATPase; NKA) is a heterodimeric protein comprising catalytic alpha (α-) and regulatory beta (β-) subunits. It drives active coupled transport of Na+ and K+ ions across the plasma membrane of most eukaryotic cells, including skeletal muscle cells, thereby also contributing to regulation of membrane potential. Tight control of Na+/K+ transport and of NKA is essential to maintaining ion homeostasis, excitability and thus muscle function. This thesis comprises two intervention studies investigating different supplementation protocols whose direct or indirect actions target the NKA in skeletal muscle, with the potential to modulate Na+/K+ homeostasis and enhance exercise performance. The first intervention used acute oral glucose supplementation to elevate endogenous insulin, thereby stimulating skeletal muscle NKA activity and modifying K+ homeostasis, under conditions of rest and intense exercise. The second intervention involved chronic sodium bicarbonate ingestion during training, as induced metabolic alkalosis is expected to increase NKA activity in skeletal muscle and lower circulating K+. The third and final study had a methodological focus using immunofluorescence techniques. This study investigated cellular distribution patterns of the NKA isoforms in human skeletal muscle cells and their localisation, contrasting the plasma membrane and intracellular regions, as well as fibre-type differences.
25
Walker, Emily. "Energy Requirements and Body Composition of Professional Team-Sport Athletes." Thesis, 2016. https://vuir.vu.edu.au/34303/.
Full textAbstract:
Team sports include repeated bouts of high-intensity activity interspersed with periods of low-intensity activity, contacts and skill execution. Optimal energy and nutrient intake is necessary for development, health, performance and for body composition goals in athletes.
26
Sostaric, Simon. "Alkalosis and digoxin effects on plasma potassium, ionic homeostasis and exercise performance in healthy humans." Thesis, 2012. https://vuir.vu.edu.au/19414/.
Full textAbstract:
Muscle contractions induce cellular potassium (K+) efflux which may contribute to
impaired muscle cell membrane excitability and fatigue. The magnitude of K+ changes
are dependent on the size of contracting muscle mass, duration and intensity of
exercise, and health and fitness status of participants. Activation of the sarcolemmal
and t-tubular bound sodium-potassium adenosine 5’ triphosphatase enzyme
(Na+,K+ATPase, NKA) mediates muscle cell K+ and Na+ active exchange, and is
instrumental in the maintenance of muscle cellular and plasma K+ homeostasis during
exercise. Therefore modulations of NKA function might enhance or impair exercise
induced K+ disturbances, and theoretically can have a profound effect on muscle
excitability and exercise performance. This thesis examined the effects of two
interventions designed to induce acute or short term upregulation and downregulation
of NKA activity on K+ homeostasis and exercise performance in healthy humans. Study
1 investigated the effects of metabolically induced alkalosis on plasma K+ regulation
during submaximal finger flexion (small muscle mass) contractions and fatigue in
healthy humans. Study 2 investigated the effects of a clinically relevant dose of digoxin
administration on K+ regulation, during intermittent supramaximal finger flexion
contractions (small muscle mass) and fatigue in healthy humans. Study 3 investigated
the effects of digoxin on K+ regulation during progressive increasing intensity
submaximal leg cycling exercise (large muscle mass) and fatigue in the same healthy
participants as in study 2. A secondary focus of this thesis was to examine the ionic,
metabolic and acid-base disturbances during small and large muscle mass exercise
and in recovery. This included the regulatory role of NKA in active (study 1 and 2) and
inactive tissue (study 3), during small (study 1 and 2) and large (study 3) muscle mass
exercise.
27
McGinley, Cian. "Effects of high-intensity training on components of muscle pH regulation." Thesis, 2015. https://vuir.vu.edu.au/31023/.
Full textAbstract:
Regulation of pH in skeletal muscle comprises intracellular buffering of hydrogen ions (H+) and acid/base (H+/HCO3−) transport across the sarcolemma. During high-intensity exercise H+ transport is primarily lactate-coupled through the monocarboxylate transporters (MCT)1/4, with non-lactate-coupled transport provided by the sodium/hydrogen exchanger (NHE) system. The chaperone protein basigin is essential for MCT functioning. Intracellular buffering comprises metabolic and physicochemical buffering (βm), the latter mainly from the histidine-based proteins and dipeptides, and inorganic phosphate. The sodium-coupled bicarbonate transport proteins (NCBT) enhance intracellular buffering and H+ efflux, while the cytosolic and sarcolemmal carbonic anhydrase (CA) isozymes may enhance activity of each transport system by physical or functional interactions.
28
Broatch, James. "The Influence of Cold-Water Immersion on the Adaptive Response to High-Intensity Interval Training in Human Skeletal Muscle." Thesis, 2015. https://vuir.vu.edu.au/30177/.
Full textAbstract:
Despite a lack of understanding of the underlying mechanisms, cold-water immersion (CWI) is extensively used by athletes for recovery. Previous evidence demonstrates its effectiveness in reducing muscle soreness, with the effects on muscle function unclear (260). Given the subjective nature of soreness, the efficacy of post-exercise CWI may be confounded by a potential placebo effect. Debate also exists surrounding the merit of CWI in athletic training regimes. While better recovery may improve subsequent training quality and stimulus (490), there is suggestion that CWI may attenuate long-term skeletal muscle adaptations (523). Conversely, CWI may stimulate the expression of genes key to mitochondrial biogenesis (192). To fully understand the mechanisms underlying CWI, and its influence on athletic performance, it is crucial to investigate these issues further. This thesis firstly aimed to investigate if the placebo effect is responsible for any short-term performance or psychological benefits following post-exercise CWI. To assess this, CWI was compared with a placebo and thermo-neutral control condition in the recovery from a single bout of high-intensity interval training (HIT). A recovery placebo was shown to be superior in the recovery of muscle strength over 48 h as compared with a control, and as effective as CWI, attributed to improved psychological ratings of well-being. This suggests that the placebo effect may account for some of the observed benefits following CWI, or alternately, that it is as strong as the commonly-hypothesised physiological benefits.
For the remaining studies, this thesis aimed to investigate the underlying molecular mechanisms by which CWI may alter cellular signalling and the long-term adaptive response to HIT in human skeletal muscle. It was demonstrated that CWI augments the post-exercise response of a number of signalling proteins and genes associated with mitochondrial adaptations. The oxidative stress imposed by CWI may serve to augment p53 activation post-exercise, leading to a greater up-regulation of its downstream targets. However, despite these alterations in cellular signalling, regular post-exercise CWI did not promote an improved adaptive response to HIT, as measured by markers of mitochondrial biogenesis and other aerobic adaptations.
29
Betteridge, Scott Sheng-Yi. "The role of nitrates in skeletal muscle metabolism during contraction." Thesis, 2016. https://vuir.vu.edu.au/30987/.
Full textAbstract:
Inorganic nitrate (NO3-) is a chemical compound found naturally in some foods, mainly green leafy vegetables. Traditionally this anion was considered inert in the human body, but recently the consumption of dietary NO3- has been shown to result in a number of positive physiological effects. These effects include protection against ischaemic reperfusion injury and improvements in glucose regulation in diabetic animal models. Some studies have also shown a reduction in blood pressure and a decrease in oxygen consumption (VO2) for a given sub-maximal exercise workload, i.e. an increase in exercise efficiency after both acute, and chronic NO3- ingestion.
30
Timpani, Cara. "Characterising and evaluating the efficacy of metabolic therapies for the treatment of Duchenne Muscular Dystrophy." Thesis, 2017. https://vuir.vu.edu.au/34336/.
Full textAbstract:
Duchenne Muscular Dystrophy (DMD) is a fatal skeletal muscle wasting
disease underpinned by extensive metabolic dysfunction. This culminates in
reduced energy production which is detrimental to dystrophic muscle since
buffering damage and stimulating repair are energy dependent processes.
Current treatment options for DMD are limited and do not address this
metabolic dysfunction despite the extensive role it plays in DMD pathogenesis
and disease progression. Therefore, this thesis investigated the efficacy of two
metabolic therapies, sodium nitrate and adenylosuccinic acid (ASA), to improve
skeletal muscle metabolism and architecture in the well-established mdx mouse
model of DMD, and in immortalised myoblasts derived from DMD patients.
31
(10725291), Priya Prakash. "Characterizing Microglial Response to Amyloid: From New Tools to New Molecules." Thesis, 2021.
Find full textAbstract:
Microglia are a population of specialized, tissue-resident immune cells that make up around 10% of total cells in our brain. They actively prune neuronal synapses, engulf cellular debris, and misfolded protein aggregates such as the Alzheimer’s Disease (AD)-associated amyloid-beta (Aβ) by the process of phagocytosis. During AD, microglia are unable to phagocytose Aβ, perhaps due to the several disease-associated changes affecting their normal function. Functional molecules such as lipids and metabolites also influence microglial behavior but have primarily remained uncharacterized to date. The overarching question of this work is, How do microglia become dysfunctional in chronic inflammation? To this end, we developed new chemical tools to better understand and investigate the microglial response to Aβ in vitro and in vivo. Specifically, we introduce three new tools. (1) Recombinant human Aβ was developed via a rapid, refined, and robust method for expressing, purifying, and characterizing the protein. (2) A pH-sensitive fluorophore conjugate of Aβ (called AβpH) was developed to identify and separate Aβ-specific phagocytic and non-phagocytic glial cells ex vivo and in vivo. (3) New lysosomal, mitochondrial, and nuclei-targeting pH-activable fluorescent probes (called LysoShine, MitoShine, and NucShine, respectively) to visualize subcellular organelles in live microglia. Next, we asked, What changes occur to the global lipid and metabolite profiles of microglia in the presence of Aβ in vitro and in vivo? We screened 1500 lipids comprising 10 lipid classes and 700 metabolites in microglia exposed to Aβ. We found significant changes in specific lipid classes with acute and prolonged Aβ exposure. We also identified a lipid-related protein that was differentially regulated due to Aβ in vivo. This new lipid reprogramming mechanism “turned on” in the presence of cellular stress was also present in microglia in the brains of the 5xFAD mouse model, suggesting a generic response to inflammation and toxicity. It is well known that activated microglia induce reactive astrocytes during inflammation. Therefore, we asked, What changes in proteins, lipids, and metabolites occur in astrocytes due to their reactive state? We provide a comprehensive characterization of reactive astrocytes comprising 3660 proteins, 1500 lipids, and 700 metabolites. These microglia and astrocytes datasets will be available to the scientific community as a web application. We propose a final model wherein the molecules secreted by reactive astrocytes may also induce lipid-related changes to the microglial cell state in inflammation. In conclusion, this thesis highlights chemical neuroimmunology as the new frontier of neuroscience propelled by the development of new chemical tools and techniques to characterize glial cell states and function in neurodegeneration.
32
Hedges, Christopher. "The effects of physiological acidosis on skeletal muscle mitochondrial function, ROS balance, and intracellular signalling." Thesis, 2017. https://vuir.vu.edu.au/35976/.
Full textAbstract:
Mitochondrial adaptation in skeletal muscle is promoted by a diverse array of stimuli, and changes in mitochondrial plasticity have been noted as a result of a many exercise modalities. High-intensity interval training is one such modality that promotes mitochondrial adaptation in response to repeated short-duration bouts of intense effort. Another result of intense muscular effort is a decrease in muscle pH, resulting in intracellular acidosis. The effect of this acidosis on oxygen consumption in muscle has received attention previously, with mixed findings. An aspect of skeletal muscle mitochondrial function that has received limited attention is the production of reactive oxygen species. To date a small number of studies have also provided evidence that attenuating the development of intracellular acidosis may have beneficial effects for mitochondrial adaptation.
This thesis aimed to further investigate the effect of acidosis on mitochondrial function, and on intracellular signalling for mitochondrial biogenesis.
33
Wallis, Amy. "Microbiota-Gut-Brain Interactions in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Focus on Neuropsychological Symptoms and Sex Comparisons." Thesis, 2017. https://vuir.vu.edu.au/37869/.
Full textAbstract:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic,
disabling condition with debilitating fatigue and neuroimmune symptoms. Consensus about
diagnosis, pathogenesis and efficacious treatments for ME/CFS are yet to be elucidated.
Advances in the understanding of microbiota-gut-brain interactions in healthy and disease
states, combined with evidence of gastrointestinal symptoms and gut dysbiosis in individuals
with ME/CFS has directed investigation towards the role of enteric microbiota in this
condition. The body of work presented in this thesis includes five publications based on
reviews and empirical research conducted over the past 3.5 years.
The first review paper (Paper 1) found preliminary evidence to support the proposal
that microbiota-gut-brain interactions may contribute to sleep, mood and cognitive symptoms
but revealed gaps in knowledge with few empirical studies that have investigated commensal
microbiota in patients with ME/CFS. Papers 2 and 3 describe the results of a correlational
analyses between microbiota and ME/CFS symptoms in a cross-sectional, retrospective study
of 274 ME/CFS patients. A notable finding from this study included sex-specific interactions
between gut microbiota and symptom expression in ME/CFS, signaling possible sex
differences in microbial function.
The systematic review examining symptom and etiological overlap between D-lactic
acidosis and ME/CFS in Paper 4, revealed preliminary support for the hypothesis that
subclinical concentrations of D-lactate from bacterial dysbiosis may be a mechanism
contributing to several ME/CFS symptoms (including fatigue, neurocognitive impairments,
pain, sleep disturbances, motor disturbances, gastrointestinal abnormalities, cardiovascular,
respiratory, thermostatic, and comorbid mood and behavioural disturbances). The review
highlighted the gaps in knowledge without measurement of D-lactate concentrations in
ME/CFS samples.
Paper 5 presents the results of an open-label, repeated-measures trial examining the
efficacy of a 4-week treatment (alternate weeks of Erythromycin and D-lactate free probiotic)
for an overgrowth of commensal Streptococcus species in 44 adult patients with ME/CFS.
Large time effects were shown including a reduction in Streptococcus count and
improvement on several clinical outcomes (sleep, cognition and total symptoms) for the total
sample at post intervention. Ancillary results highlighted individual variability in microbial
changes and the importance of other genera with changes in Bacteroides, Bifidobacteria and
Clostridium and associated with clinical changes in males.
In combination, the analysis of literature and results from both cross-sectional and
experimental studies substantiate the theoretical premise that microbiota and gut dysbiosis
contribute to specific neuropsychological symptoms in some ME/CFS patients. Our
mechanistic understanding of gut dysbiosis will be advanced by multidisciplinary
investigations that include assessment of clinical symptoms, the microbiome (combined
sequencing and culture techniques), metabolites, oxidative and inflammatory markers, and
immune profiles that help identify possible factors contributing to, precipitating or
perpetuating imbalances in microbial composition. These advances may help clarify
diagnostic discrepancies and inform efficacious treatment alternatives that are responsive to
individual variability.
34
Christiansen, Danny. "Promoting training adaptation in human skeletal muscle by blood flow restriction and cold-water immersion: with special emphasis on K+ regulation and Na+,K+-ATPase abundance in different fibre types." Thesis, 2018. https://vuir.vu.edu.au/38640/.
Full textAbstract:
The molecular signals underlying improvements in the skeletal muscle capacity for K+ regulation and
Na+,K+-ATPase expression in humans are poorly understood. Further, fibre-type-specific regulation
of Na+,K+-ATPase isoforms by exercise training appears inadequately explored. This thesis
investigated in humans possible mechanisms regulating the muscle’s capacity for K+ regulation and
Na+,K+-ATPase-isoform expression in different fibre types with exercise training and presents a novel
method for fibre type identification of single muscle fibres. Molecular signals (oxidative stress,
hypoxia, lactate, AMPK- and Ca2+-signalling) were modulated by exercising with and without blood
flow restriction (BFR), and in systemic hypoxia, and changes in expression of Na+,K+-ATPase genes
were examined by RT-PCR. In another experiment, an intra-subject design was used, where one
leg trained with and the other leg without BFR, along with measurement of thigh K+ release. Effects
of cold-water immersion on training-induced adaptations in Na+,K+-ATPase isoforms were also
examined. The reliability and validity of dot blotting for fibre-type determination of single muscle fibres
were evaluated by use of western blotting. Key findings were that increased oxidative stress, AMPK
signalling, and disturbance of ionic and redox homeostasis are positively associated with training-induced
increases in the capacity for K+ regulation and Na+,K+-ATPase-isoform expression. In
contrast, the level of hypoxia and lactate concentration, and modulation of CaMKII signalling, was
not related to the regulation of Na+,K+-ATPase-isoform expression. Fibre type-dependent
adaptations of Na+,K+-ATPase expression were associated with improvements in K+ regulation and
exercise tolerance. In addition, dot blotting was valid and reliable for fibre type determination of single
muscle fibres. In conclusion, this thesis has identified key mechanisms underlying, and a novel
strategy (BFR training) to augment, training-induced improvements in K+ regulation by human
skeletal muscle and presents a valid and reliable method for easy and rapid fibre type determination
of individual muscle fibres.
35
Manikkam, Vasambal. "In-vitro physiological activities of peptides derived from underutilised Australian fish species." Thesis, 2016. https://vuir.vu.edu.au/32739/.
Full textAbstract:
Australian underutilised fish species, such as silver warehou (Seriollela punctata)
and eastern school whiting (Sillago flindersi) as well as fish by-products may be potent
sources of bioactive peptides. These species and/or their by-products are often wasted due
to their poor technological and textural properties, and not acceptable for consumption by
the Australian consumers. Interestingly, these fish wastes possess important nutritional
value and physiological benefits, owing to their high protein content. Technological
processing and the presence of endogenous enzymes in the fish muscle have the potential
to release the so-called bioactive peptides during storage or digestion in the
gastrointestinal tract. In the new era of the field of food science and technology, the
production of bioactive peptides released from fish wastes is becoming increasingly
important to preserve the marine sustainable environment and develop essential
functional food to maintain human health as well as preventing the risks of developing
certain types of metabolic diseases, like obesity and/or metabolic syndrome.
As a result, the main focus of this project was to investigate the controlled
hydrolysis of fish muscle proteins from by-catch fish species as a means of producing
bioactive peptides with beneficial physiological properties. Important in-vitro
bioactivities investigated could be related to the prevention of obesity and associated
health complications. They include i) angiotensin-converting enzyme (ACE –
hypertension) inhibition, ii) trypsin inhibition (satiety-induced) and iii) anti-oxidative
(oxidative stress and inflammation-related conditions) activity.
36
Manuelpillai, Usula Chandini. "Expression and effects of epidermal growth factor related peptides in human term gestational tissue." Thesis, 1999. https://vuir.vu.edu.au/16133/.
Full textAbstract:
This thesis w a s undertaken to détermine the expression of several growth factors that
belong to the Epidermal Growth Factor ( E G F ) family in h u m a n term gestational tissue. It
also examines the effects exerted by Transforming Growth Factor alpha (TGFa), a
member of the E G F family, on cultured villous cytotrophoblast (CT) cells isolated from
placentae delivered between 38-40 weeks gestation.
37
Parker, Lewan. "Exercise intensity and glycaemic control : the role of redox status and redox-sensitive protein kinase signalling in humans." Thesis, 2017. https://vuir.vu.edu.au/34047/.
Full textAbstract:
Physical inactivity and obesity are associated with elevated systemic oxidative
stress and the activation of JNK, p38 MAPK, NF-κB, and protein kinase C (PKC)
signalling pathways in skeletal muscle. Sustained activation of these stress and
mitogen activated protein kinase (SAPK) pathways are associated with impaired
glycaemic control, and the development and progression of cardiometabolic
disease. Paradoxically, acute exercise also increases oxidative stress and SAPK
signalling, yet glycaemic control and skeletal muscle function are enhanced.
Research now supports a role for the transient induction of oxidative stress and
associated activation of SAPK signalling in the physiological response and
adaptation to acute exercise and exercise training. High-intensity interval
exercise (HIIE) is a potent exercise stimulus for the improvement of metabolic
health and skeletal muscle adaption, however the effect of HIIE on oxidative
stress and SAPK signalling is unclear. The aims of this thesis were to explore the
effect of HIIE on glycaemic control, exercise-induced oxidative stress, and
skeletal muscle SAPK signalling, in a series of independent but related studies.
38
Oliveira, Filippe. "Like father, like daughter: Can maternal or early life exercise break the cycle of paternal diet-induced metabolic programming in female offspring?" Thesis, 2017. https://vuir.vu.edu.au/34721/.
Full textAbstract:
...the aim of this research was to investigate if maternal exercise (Chapter 3) or offspring early in life exercise (Chapter 4) could attenuate the negative metabolic consequences in adult rat offspring sired by high-fat fed obese fathers (Chapter 3 and 4).
39
Astell, Katie J. "Effects of Caralluma fimbriata extract on cardiovascular and metabolic disorders." Thesis, 2016. https://vuir.vu.edu.au/33252/.
Full textAbstract:
Central obesity, insulin resistance, atherogenic dyslipidemia and elevated blood pressure are the major components of metabolic syndrome. This complex disorder is considered to be a clinical challenge and an urgent public health issue. With the growing prevalence of obesity worldwide, effective strategies are needed to intervene in the development and progression of metabolic syndrome. Despite the short-term benefits of pharmaceutical treatment of obesity, current drug therapy is associated with adverse side effects, thus the use of complementary and alternative therapies has become increasingly popular among the general population as an alternative method for weight loss. Botanical extracts in combination with lifestyle modification may be effective agents for attenuating the development of metabolic syndrome as they often comprise of a vast range of bioactive compounds that have been associated with significant positive health outcomes with minimal side effects. However, the efficacy of many of these extracts and their chemical constituents have yet to be fully explored. The research presented in this thesis examines the effectiveness of two commonly used anti-obesity botanical extracts, namely Caralluma fimbriata and Citrus sinensis (Moro variety). The primary aim of this PhD project was to investigate the efficacy of C. fimbriata extract on the risk factors of metabolic syndrome in overweight and obese conditions.
40
Cassar, Samantha. "Polycystic Ovary Syndrome, Obesity and Insulin Resistance." Thesis, 2014. https://vuir.vu.edu.au/30172/.
Full textAbstract:
Polycystic ovary syndrome (PCOS) is a common and complex reproductive and metabolic
condition with major health consequences across the lifespan. Insulin resistance is thought to
be a key underlying feature of PCOS, but its role in metabolic and reproductive
complications associated with the syndrome remains elusive. Therefore, the aim of the thesis
was to comprehensively assess the role of IR in PCOS. I report that IR is definitively intrinsic
to PCOS and exacerbated by BMI. But the effect of BMI on IR is more pronounced in PCOS
than controls. Diagnostic criteria and age seem to have little effect on IR in PCOS.
Furthermore, IR in PCOS seems to be negatively correlated with testosterone and positively
correlated with sex hormone binding globulin. Gonadotropins seem to have little effect on IR.
Various biomarkers associated with metabolic diseases appear more strongly associated with
obesity rather than with PCOS status and Plasminogen activator inhibitor-1 may also be a
novel independent biomarker with the ability to predict IR in women with and without PCOS.
This intrinsic IR in PCOS was not attributed to mitochondrial dysfunction and was not related
to the pathophysiology of reproductive dysfunction in PCOS as measured by Anti-Mullarian
hormone (AMH). However, AMH was able to detect PCOS status and may also be useful in
the diagnosis of PCOS. Collectively these chapters of related studies enhanced understanding
of IR in PCOS, including the relationship between intrinsic and extrinsic factors and IR and
provided information regarding potential markers to aid in diagnosing PCOS and IR.
41
Fu, Lulu. "Effects of kiwi-fruit seaweed extract on the metabolism of female reproductive hormones." Thesis, 2014. https://vuir.vu.edu.au/25823/.
Full textAbstract:
Hormonal fluctuations are known to affect a female’s quality of life during the different stages of their lifespan. In middle-aged women, hormonal fluctuations are especially known to impact on their mental and physical health. During the peri- menopausal years, a woman’s health can deteriorate and unfortunately may eventuate in severe diseases.
The perspective on conventional and Chinese medicine is that there are interventions available for hormone-related diseases. Within the conventional medical field, little is known about the interventions available within Chinese medicine (CM) practice and even less is known of the efficiency of Chinese Medicine interventions, even within the Chinese medicine practice. Conventional Medicine and Chinese medicine both rely on diagnosis as a pre-requisite to prescribing intervention. However, the main difference between the two medical fields is that diagnosis in Chinese medicine relies on patterns of dysfunction of the Chinese medicine organ systems, rather than any underlying causes explained in terms of a pathophysiological malfunction.
The aim of this research was to investigate the effects of a Chinese food formula, Kiwi-Fruit Seaweed Extract (KFE), on the regulation of the biomarker 2-hydroxyoestrone:16α-hydroxyoestrone, relating to thermography changes and magnetic field changes in the woman’s breast. The magnetic field changes which indicated by the pulsed electromagnetic field test overlaid the Liver Meridian, Kidney Meridian and other Meridians in the trunk area as described from the Chinese medicine perspective. This study also examined the general improvement and emotional impact of KFE on women with Liver Qi Stagnation and Liver Kidney Yin Deficiency.