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CLINICAL AND EXPERIMENTAL EVIDENCE FOR THE PATHOLOGICAL MECHANISMS UNDERLYING ASPECTS OF SEXUAL DYSFUNCTION: IMPACT OF ADIPOSITY AND CHRONIC KIDNEY DISEASEMaio Twofoot, Maria Tina 01 October 2013 (has links)
Cardiovascular disease (CVD) and erectile dysfunction (ED) have common etiologies, such as increased adiposity and chronic diseases. Incident ED is known to be a sentinel of CVD, providing a unique opportunity for early lifestyle interventions to attenuate the progression of disease. The internal pudendal artery (IPA) plays an important role in controlling resistance to penile blood flow and thereby erections. Although morphological and functional disturbances in the IPA have been associated with ED, few studies have characterized changes in the IPA as it relates to increased adiposity and chronic diseases (e.g., chronic kidney disease [CKD]). Finally, although both vascular calcification and ED have been shown to be prevalent in patients with CKD, there has yet to be an assessment of associated mechanisms.
The effect of lifestyle modifications on erectile function was evaluated in both experimental and clinical settings. Specifically, the studies assessed the effect of caloric restriction (CR) in rats and of chronic exercise in sedentary, overweight or obese male and female subjects. In rats, structural and functional changes of the IPA and erectile responses were characterized in relation to increasing adiposity and to CKD. Experimentally, the susceptibility of various vascular beds to calcification in CKD was determined. Clinically, erectile and female sexual function was assessed in patients with Stage 3 to 5 CKD, who had no history of CVD.
In rats, CR blunted the accumulation of abdominal adiposity, and attenuated progression of both endothelial dysfunction and ED, independently of morphological changes in the IPA. Rats with CKD had an increased frequency of ED, greater endothelial dysfunction, and altered vascular morphology, yet vascular calcification per se did not account for ED.
In the clinical study, sedentary and overweight or obese males with ED, but not females, had a significantly higher body mass index (BMI) and waist circumference. Chronic exercise significantly improved ED and female sexual dysfunction (FSD). Clinically, CKD was associated with ED and FSD as well as increased coronary artery calcification and endothelial dysfunction.
These findings support the concept that early detection of cardiovascular abnormalities, using incident ED as a sentinel, should facilitate early interventions in otherwise asymptomatic populations. / Thesis (Ph.D, Pharmacology & Toxicology) -- Queen's University, 2013-09-30 22:33:20.436
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Efeitos da suplementação do ácido graxo alfa-linolênico (ALA) no metabolismo e no estresse do retículo endoplasmático em tecido adiposo visceral de obeso grau III / Alpha-linolenic acid supplementation effects on endoplasmic reticulum stress in visceral adipose tissue from morbid obese patientsMariana Pinto Chaves 06 December 2017 (has links)
Atualmente, a obesidade é considerada uma epidemia mundial. Está associada a um estado de inflamação crônica e ativação do estresse do retículo endoplasmático (ERE), relacionados à patogênese de diversas doenças como diabetes mellitus tipo 2, doenças cardiovasculares, câncer, hipertensão, dentre outras. Nesse contexto, são necessários estudos para encontrar alternativas que melhorem o processo inflamatório. Vários estudos em humanos e animais já demostraram as propriedades anti-inflamatórias do ácido graxo ômega-3. O objetivo do nosso trabalho foi avaliar os efeitos da suplementação do ácido alfa-linolênico (ALA) no metabolismo e no estresse do retículo endoplasmático em obesos grau III. Foi conduzido um estudo prospectivo, randomizado, placebo-controlado, duplo-cego. No total, 52 pacientes foram randomizados para a suplementação com 3g/dia de ALA ou placebo, sendo 27 indivíduos do grupo ômega-3/ALA e 25 do grupo controle. Foi avaliado perfil lipídico, glicídico e inflamatório antes e após suplementação. O tecido adiposo visceral (TAV) foi coletado durante cirurgia bariátrica após suplementação. O perfil de ácidos graxos incorporados no TAV foi avaliado por cromatografia gasosa. Os genes foram avaliados através de PCR em tempo real. Não houve alteração nos níveis séricos de IL-6 (p=0,2201), TNF-? (0.7703) e PCR (p=0,57) após suplementação com ômega-3/ALA, porém observamos diminuição nos níveis séricos de Leptina (p=0.0154) e IP-10 (p=0.0410), citocinas inflamatórias, e aumento na IL-4 (p=0,0211), citocina anti-inflamatória. Foi observado incorporação significativa do ALA (p=0,0002), EPA (p<0,0001) e DHA (p=0,0005) no TAV. Avaliação molecular evidenciou um aumento da expressão gênica do XBP1 (p=0,0013), sXBP1 (p<0,0001), EIF2-? (p=0,0063) e da chaperona CCT4 (p=0,0001) e diminuição na expressão gênica da leptina (p=0,0410). Podemos concluir que o ALA pode modular o ERE através da via da IRE1/XBP, levando ao aumento das chaperonas (CCT4), o que pode demonstrar um potencial terapêutico do ALA em pacientes obesos. / Currently, obesity is considered a worldwide epidemic. It is associated with chronic inflammation and stress activation of the endoplasmic reticulum (ERE), related to the pathogenesis of various diseases such as type 2 diabetes mellitus, cardiovascular diseases, cancer, hypertension, among others. In this context, studies are needed to find alternatives that improve the inflammatory process. Several studies in humans and animals have already demonstrated the anti-inflammatory properties of omega-3 fatty acid. The objective of our study was to evaluate the effects of alpha-linolenic acid (ALA) supplementation on the metabolism and stress of the endoplasmic reticulum in obese patients. A prospective, randomized, placebo-controlled, double-blind study was conducted. In total, 52 patients were randomized to supplementation with 3 g / day of ALA or placebo, 27 individuals from the omega-3 / ALA group and 25 from the control group. Lipid, glycidic and inflammatory profile were evaluated before and after supplementation. Visceral adipose tissue (TAV) was collected during bariatric surgery after supplementation. The fatty acid profile incorporated in the TAV was evaluated by gas chromatography. Genes were evaluated by real-time PCR. There was no change in serum levels of IL-6 (p = 0.2201), TNF-? (0.7703) and CRP (p = 0.57) after supplementation with ALA, but we observed a decrease in serum Leptin levels (P = 0.0154) and IP-10 (p = 0.0410), inflammatory cytokines, and increase in IL-4 (p = 0.0211), anti-inflammatory cytokine. Significant incorporation of ALA (p = 0.0002), EPA (p <0.0001) and DHA (p = 0.0005) into the TAV was observed. Molecular evaluation showed an increase in the gene expression of XBP1 (p = 0.0013), sXBP1 (p <0.0001), EIF2-? (p = 0.0063), GADD34 (p=0,0117) and CCT4 chaperone (p = 0.0001), decrease in the gene expression of leptin (p = 0.0410) and ATF-6 (p=0,0305) and a tendency to decrease the gene expression of CHOP. We can conclude that ALA can modulate ERE through the IRE1 / XBP, PERK and ATF-6 pathways, leading to increased chaperones (CCT4), which may demonstrate a therapeutic potential of ALA in obese patients.
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Efeitos da suplementação do ácido graxo alfa-linolênico (ALA) no metabolismo e no estresse do retículo endoplasmático em tecido adiposo visceral de obeso grau III / Alpha-linolenic acid supplementation effects on endoplasmic reticulum stress in visceral adipose tissue from morbid obese patientsChaves, Mariana Pinto 06 December 2017 (has links)
Atualmente, a obesidade é considerada uma epidemia mundial. Está associada a um estado de inflamação crônica e ativação do estresse do retículo endoplasmático (ERE), relacionados à patogênese de diversas doenças como diabetes mellitus tipo 2, doenças cardiovasculares, câncer, hipertensão, dentre outras. Nesse contexto, são necessários estudos para encontrar alternativas que melhorem o processo inflamatório. Vários estudos em humanos e animais já demostraram as propriedades anti-inflamatórias do ácido graxo ômega-3. O objetivo do nosso trabalho foi avaliar os efeitos da suplementação do ácido alfa-linolênico (ALA) no metabolismo e no estresse do retículo endoplasmático em obesos grau III. Foi conduzido um estudo prospectivo, randomizado, placebo-controlado, duplo-cego. No total, 52 pacientes foram randomizados para a suplementação com 3g/dia de ALA ou placebo, sendo 27 indivíduos do grupo ômega-3/ALA e 25 do grupo controle. Foi avaliado perfil lipídico, glicídico e inflamatório antes e após suplementação. O tecido adiposo visceral (TAV) foi coletado durante cirurgia bariátrica após suplementação. O perfil de ácidos graxos incorporados no TAV foi avaliado por cromatografia gasosa. Os genes foram avaliados através de PCR em tempo real. Não houve alteração nos níveis séricos de IL-6 (p=0,2201), TNF-? (0.7703) e PCR (p=0,57) após suplementação com ômega-3/ALA, porém observamos diminuição nos níveis séricos de Leptina (p=0.0154) e IP-10 (p=0.0410), citocinas inflamatórias, e aumento na IL-4 (p=0,0211), citocina anti-inflamatória. Foi observado incorporação significativa do ALA (p=0,0002), EPA (p<0,0001) e DHA (p=0,0005) no TAV. Avaliação molecular evidenciou um aumento da expressão gênica do XBP1 (p=0,0013), sXBP1 (p<0,0001), EIF2-? (p=0,0063) e da chaperona CCT4 (p=0,0001) e diminuição na expressão gênica da leptina (p=0,0410). Podemos concluir que o ALA pode modular o ERE através da via da IRE1/XBP, levando ao aumento das chaperonas (CCT4), o que pode demonstrar um potencial terapêutico do ALA em pacientes obesos. / Currently, obesity is considered a worldwide epidemic. It is associated with chronic inflammation and stress activation of the endoplasmic reticulum (ERE), related to the pathogenesis of various diseases such as type 2 diabetes mellitus, cardiovascular diseases, cancer, hypertension, among others. In this context, studies are needed to find alternatives that improve the inflammatory process. Several studies in humans and animals have already demonstrated the anti-inflammatory properties of omega-3 fatty acid. The objective of our study was to evaluate the effects of alpha-linolenic acid (ALA) supplementation on the metabolism and stress of the endoplasmic reticulum in obese patients. A prospective, randomized, placebo-controlled, double-blind study was conducted. In total, 52 patients were randomized to supplementation with 3 g / day of ALA or placebo, 27 individuals from the omega-3 / ALA group and 25 from the control group. Lipid, glycidic and inflammatory profile were evaluated before and after supplementation. Visceral adipose tissue (TAV) was collected during bariatric surgery after supplementation. The fatty acid profile incorporated in the TAV was evaluated by gas chromatography. Genes were evaluated by real-time PCR. There was no change in serum levels of IL-6 (p = 0.2201), TNF-? (0.7703) and CRP (p = 0.57) after supplementation with ALA, but we observed a decrease in serum Leptin levels (P = 0.0154) and IP-10 (p = 0.0410), inflammatory cytokines, and increase in IL-4 (p = 0.0211), anti-inflammatory cytokine. Significant incorporation of ALA (p = 0.0002), EPA (p <0.0001) and DHA (p = 0.0005) into the TAV was observed. Molecular evaluation showed an increase in the gene expression of XBP1 (p = 0.0013), sXBP1 (p <0.0001), EIF2-? (p = 0.0063), GADD34 (p=0,0117) and CCT4 chaperone (p = 0.0001), decrease in the gene expression of leptin (p = 0.0410) and ATF-6 (p=0,0305) and a tendency to decrease the gene expression of CHOP. We can conclude that ALA can modulate ERE through the IRE1 / XBP, PERK and ATF-6 pathways, leading to increased chaperones (CCT4), which may demonstrate a therapeutic potential of ALA in obese patients.
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Assessment of Body Composition Using Magnetic Resonance ImagingKullberg, Joel January 2007 (has links)
<p>Methods for assessment of body composition allow studies of the complex relationships between body composition and the wellbeing of humans. The amount and distribution of adipose tissue is of great importance in these studies. This thesis describes, proposes, and evaluates new methods for assessment of body composition (amount and distribution of adipose tissue) using magnetic resonance imaging (MRI). The thesis focuses on the use of MRI but includes results from computed tomography (CT) and dual energy X-ray absorptiometry (DEXA). The subject data used originates from cohorts recruited solely for the purpose of the included studies and from the “Prospective Investigation of Vasculature in Uppsala Seniors” (PIVUS) and the Sib-pair (within the framework of the Swedish Obese Subjects - SOS study) studies.</p><p>The included studies propose a new acquisition method for whole-body analysis of adipose tissue, a fully automated post processing algorithm for segmentation of visceral and subcutaneous adipose tissue from abdominal MRI data, and anthropometrical measurements for practical estimations of body composition.</p><p>The proposed acquisition method for whole-body adipose tissue analysis simplified the analysis of adipose tissue and the results strongly correlated with the results from CT and DEXA analysis. The fully automated post processing algorithm gave reproducible results with relatively high accuracy. Transverse and sagittal abdominal diameters gave information about subcutaneous and visceral adipose tissue, respectively, and an elliptical approximation was found useful in estimation of total amount of abdominal adipose tissue.</p><p>The methods proposed in this thesis were found useful for assessment of body composition. The methods were developed with clinical practice in mind and all proposed methods have been used in further studies for assessment of body composition.</p>
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Assessment of Body Composition Using Magnetic Resonance ImagingKullberg, Joel January 2007 (has links)
Methods for assessment of body composition allow studies of the complex relationships between body composition and the wellbeing of humans. The amount and distribution of adipose tissue is of great importance in these studies. This thesis describes, proposes, and evaluates new methods for assessment of body composition (amount and distribution of adipose tissue) using magnetic resonance imaging (MRI). The thesis focuses on the use of MRI but includes results from computed tomography (CT) and dual energy X-ray absorptiometry (DEXA). The subject data used originates from cohorts recruited solely for the purpose of the included studies and from the “Prospective Investigation of Vasculature in Uppsala Seniors” (PIVUS) and the Sib-pair (within the framework of the Swedish Obese Subjects - SOS study) studies. The included studies propose a new acquisition method for whole-body analysis of adipose tissue, a fully automated post processing algorithm for segmentation of visceral and subcutaneous adipose tissue from abdominal MRI data, and anthropometrical measurements for practical estimations of body composition. The proposed acquisition method for whole-body adipose tissue analysis simplified the analysis of adipose tissue and the results strongly correlated with the results from CT and DEXA analysis. The fully automated post processing algorithm gave reproducible results with relatively high accuracy. Transverse and sagittal abdominal diameters gave information about subcutaneous and visceral adipose tissue, respectively, and an elliptical approximation was found useful in estimation of total amount of abdominal adipose tissue. The methods proposed in this thesis were found useful for assessment of body composition. The methods were developed with clinical practice in mind and all proposed methods have been used in further studies for assessment of body composition.
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Evidence Linking Alterations in the Moment-to-Moment Pressure-Natriuresis Mechanism to Hypertension and Salt-Sensitivity in RodentsKomolova, Marina 13 May 2010 (has links)
Hypertension and salt-sensitivity are independent risk factors for cardiovascular disease. Although both conditions are idiopathic, they develop due to a complex interplay between susceptibility genes and environmental factors. Given that the kidney plays an important role in regulating blood pressure, in particular, by maintaining sodium and water balance via pressure-natriuresis, it is not surprising that disturbances in the proper functioning of this intrarenal mechanism have been linked to these conditions. Although direct coupling of changes in renal arterial pressure (RAP) to renal interstitial hydrostatic pressure (RIHP) and consequent sodium excretion is well established, few studies have characterized the moment-to-moment aspects of this process. Thus, the main focus of the research presented herein was to characterize the moment-to-moment RAP-RIHP relationship, and assess the functioning of this intrarenal mechanism in various animal models of genetic and environmentally-induced hypertension and/or salt-sensitivity.
In adult normotensive rats, the response time of RIHP to acute changes in RAP was rapid (<2 seconds), and the moment-to-moment RAP-RIHP relationship was linear over a wide range of pressures. Additionally, the functioning of this relationship was not affected by inhibition of the renin-angiotensin system and autonomic nervous system. Further, the acute RAP-RIHP relationship was impaired in hypertension and/or salt-sensitivity. Specifically, animals with a hypertensive phenotype (i.e. young spontaneously hypertensive rats [SHR] and pro-atrial natriuretic peptide gene-disrupted mice [ANP -/-]) displayed a rightward shift in the moment-to-moment pressure-natriuresis curve towards higher RAP. This rightward shift was associated with increased structurally-based vascular resistance properties in the hindlimb of young SHR versus their normotensive controls. Salt-sensitive phenotypes were associated with a blunting of this acute mechanism. Specifically, this blunting was evident in both the ANP -/-, a transgenic model of salt-sensitive hypertension, and in adult perinatal iron deficient (PID) rats, a developmentally programmed model of salt-sensitivity. It appears that a blunting in the RAP-RIHP relationship is influenced by an imbalance of key blood pressure modulating factors (e.g. ANP). Further, visceral obesity was associated with salt-sensitivity in PID rats; however the mechanism(s) are yet to be elucidated. Novel methodologies (MRI, abdominal girth) were developed for non-invasive assessment of visceral obesity to aid future research. / Thesis (Ph.D, Pharmacology & Toxicology) -- Queen's University, 2010-05-12 10:11:21.197
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Investigation into the effects of a lifestyle intervention on body fat distribution and fatty acid metabolism: Study of obese non-diabetic adults and a case study of McArdle diseaseStephanie Ipavec Levasseur Unknown Date (has links)
The global epidemic of obesity is rapidly becoming a major public health problem in many parts of the world. Unhealthy diets and physical inactivity are two modifiable risk factors for prevention of obesity and its associated chronic diseases. Their influence on muscle energy metabolism and fat mass is not completely elucidated. A decreased capacity for fatty acid oxidation (FAO) may be a metabolic risk factor for weight gain and is found to be depressed in obese individuals; and exercise training may promote an increased capacity for FAO. In addition to the interest in whole-body FAO, the role of site specific lipid accumulation including visceral adipose tissue (VAT), intrahepatic lipids (IHL) and intramyocellular lipids (IMCL) has become a focus of interest because of their reported association with insulin resistance (IR), a key metabolic defect associated with obesity and type 2 diabetes mellitus (T2DM). However, ambiguity persists regarding the importance of IMCL as a metabolic substrate for energy production in obesity. A better understanding of the factors regulating FAO, body fat distribution and IMCL mobilisation is important for the development of interventions allowing effective treatment of conditions in which these are disturbed. The study of individuals with metabolic myopathies can give more information about the energy metabolism of muscle. McArdle disease (MD) affects glucose availability to muscle for energy production. Investigations into IMCL storage and mobilisation in MD have not been reported. The aims of this thesis are to investigate 1) the effects of weight-loss via dietary restriction plus modest but clinically-relevant exercise training on FAO, body fat distribution and mobilisation of IMCL during exercise in obese non-diabetic adults; 2) the effect of an exercise training intervention on IMCL storage and mobilisation in a subject with MD. All obese subjects underwent a 4 month lifestyle intervention with weekly meetings with a dietitian and an exercise physiologist. Of the 92 subjects, 73 completed the intervention. They showed significant decreases in body weight (8%), fat mass (14%) and total cholesterol (5%). The exercise prescription of 1500 kcal.week-1 resulted in variable compliance with the prescription (1224 ± 1085 kcal.week-1) measured by heart rate monitor. Those who did most exercise and also those who had less weekly variability in their exercise, had greater reductions in body weight and fat mass. The total activity energy expenditure measured by accelerometry did not change post-intervention but there was a reduction in low intensity activity and an increase in moderate and high intensity activity. A submaximal treadmill test and resting metabolic rate (RMR) using indirect calorimetry was measured before and after the intervention to investigate factors regulating FAO and energy expenditure. Subjects showed increases in FAO without change in energy expenditure for the same walking speed post intervention, but the volume of exercise completed during the intervention was not associated with these changes. To investigate body fat distribution in obesity, VAT, IHL and soleus muscle IMCL was measured in a sub-group of 18 males by magnetic resonance imaging (MRI) and spectroscopy (MRS) along with measurement of maximal aerobic capacity. Fitness increased significantly with significant decreases in VAT (29%) and IHL (54%), without significant change in IMCL. Subjects who had the greatest decrease in VAT were those who exercised for longer durations during the intervention. IHL was the only measure of excess lipid that correlated with IR. The measurement of IMCL before and after 1-hour of cycle ergometer exercise showed no significant mobilisation of IMCL either at baseline or after the lifestyle intervention. The intensity of the acute exercise was adjusted to correspond to each individual’s maximal fatty acid oxidation (MFAO) which increased by over 60% post intervention. In the subject with MD, an 8 week exercise training intervention without dietary intervention increased IMCL stores by 27%, but there was no marked change in IMCL with acute exercise at both time points. The findings of this thesis demonstrate that a clinically relevant and achievable lifestyle intervention incorporating weight loss through diet and objectively measured exercise can achieve improvements in blood lipid profile, body composition and FAO. The differential effects of the intervention on the various fat depots and their associations to metabolic markers suggest that individualised strategies may be required dependent upon body fat distribution. The non detection of mobilisation of IMCL by MRS suggests that these lipids may not be present as a substrate source in this population but rather an ectopic lipid depot related to increased energy consumption in diet. The relatively low capacity for FAO in both the obese and MD subjects may have affected the results. This thesis discusses implications for clinical practice, discusses novel findings related to the energy metabolism in obesity and MD and informs clinical and basic science about important future directions.
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Investigation into the effects of a lifestyle intervention on body fat distribution and fatty acid metabolism: Study of obese non-diabetic adults and a case study of McArdle diseaseStephanie Ipavec Levasseur Unknown Date (has links)
The global epidemic of obesity is rapidly becoming a major public health problem in many parts of the world. Unhealthy diets and physical inactivity are two modifiable risk factors for prevention of obesity and its associated chronic diseases. Their influence on muscle energy metabolism and fat mass is not completely elucidated. A decreased capacity for fatty acid oxidation (FAO) may be a metabolic risk factor for weight gain and is found to be depressed in obese individuals; and exercise training may promote an increased capacity for FAO. In addition to the interest in whole-body FAO, the role of site specific lipid accumulation including visceral adipose tissue (VAT), intrahepatic lipids (IHL) and intramyocellular lipids (IMCL) has become a focus of interest because of their reported association with insulin resistance (IR), a key metabolic defect associated with obesity and type 2 diabetes mellitus (T2DM). However, ambiguity persists regarding the importance of IMCL as a metabolic substrate for energy production in obesity. A better understanding of the factors regulating FAO, body fat distribution and IMCL mobilisation is important for the development of interventions allowing effective treatment of conditions in which these are disturbed. The study of individuals with metabolic myopathies can give more information about the energy metabolism of muscle. McArdle disease (MD) affects glucose availability to muscle for energy production. Investigations into IMCL storage and mobilisation in MD have not been reported. The aims of this thesis are to investigate 1) the effects of weight-loss via dietary restriction plus modest but clinically-relevant exercise training on FAO, body fat distribution and mobilisation of IMCL during exercise in obese non-diabetic adults; 2) the effect of an exercise training intervention on IMCL storage and mobilisation in a subject with MD. All obese subjects underwent a 4 month lifestyle intervention with weekly meetings with a dietitian and an exercise physiologist. Of the 92 subjects, 73 completed the intervention. They showed significant decreases in body weight (8%), fat mass (14%) and total cholesterol (5%). The exercise prescription of 1500 kcal.week-1 resulted in variable compliance with the prescription (1224 ± 1085 kcal.week-1) measured by heart rate monitor. Those who did most exercise and also those who had less weekly variability in their exercise, had greater reductions in body weight and fat mass. The total activity energy expenditure measured by accelerometry did not change post-intervention but there was a reduction in low intensity activity and an increase in moderate and high intensity activity. A submaximal treadmill test and resting metabolic rate (RMR) using indirect calorimetry was measured before and after the intervention to investigate factors regulating FAO and energy expenditure. Subjects showed increases in FAO without change in energy expenditure for the same walking speed post intervention, but the volume of exercise completed during the intervention was not associated with these changes. To investigate body fat distribution in obesity, VAT, IHL and soleus muscle IMCL was measured in a sub-group of 18 males by magnetic resonance imaging (MRI) and spectroscopy (MRS) along with measurement of maximal aerobic capacity. Fitness increased significantly with significant decreases in VAT (29%) and IHL (54%), without significant change in IMCL. Subjects who had the greatest decrease in VAT were those who exercised for longer durations during the intervention. IHL was the only measure of excess lipid that correlated with IR. The measurement of IMCL before and after 1-hour of cycle ergometer exercise showed no significant mobilisation of IMCL either at baseline or after the lifestyle intervention. The intensity of the acute exercise was adjusted to correspond to each individual’s maximal fatty acid oxidation (MFAO) which increased by over 60% post intervention. In the subject with MD, an 8 week exercise training intervention without dietary intervention increased IMCL stores by 27%, but there was no marked change in IMCL with acute exercise at both time points. The findings of this thesis demonstrate that a clinically relevant and achievable lifestyle intervention incorporating weight loss through diet and objectively measured exercise can achieve improvements in blood lipid profile, body composition and FAO. The differential effects of the intervention on the various fat depots and their associations to metabolic markers suggest that individualised strategies may be required dependent upon body fat distribution. The non detection of mobilisation of IMCL by MRS suggests that these lipids may not be present as a substrate source in this population but rather an ectopic lipid depot related to increased energy consumption in diet. The relatively low capacity for FAO in both the obese and MD subjects may have affected the results. This thesis discusses implications for clinical practice, discusses novel findings related to the energy metabolism in obesity and MD and informs clinical and basic science about important future directions.
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Alterações metabólicas decorrentes de dieta hiperlipídica em modelo animal não resistente à insulinaRamalho, Leticia January 2011 (has links)
Objetivo: Sabe-se que trabalhadores noturnos tem preferência por lanches com maior concentração de gordura saturada. Trabalhadores de turno, particularmente trabalhadores noturnos, apresentam mais frequentemente hipertrigliceridemia e hiperglicemia, bem como menores níveis de HDL-colesterol quando comparados a trabalhadores diurnos, devido a alterações circadianas e estilo de vida, sugerindo uma predisposição para o desenvolvimento de doenças cardiovasculares. Estas alterações são conhecidas como Síndrome Metabólica (SM). Portanto, para entender as conseqüências de uma dieta hiperlipídica é importante a padronização de dietas para modelos animais que mimetizem a alimentação do trabalhador de turno. Materiais e Método: estudo experimental com 20 ratos Wistar dos quais 10 eram controle (CG) e 10 submetidos à dieta hiperlipídica (HFD). Utilizaram-se três dos cinco critérios do NCEP-ATP III para diagnóstico de SM - glicose, triglicerídeos (TG) e HDL-col. A quantidade de tecido adiposo visceral (TAV) foi avaliada bem como o peso do fígado e das glândulas adrenais. O peso ponderal foi avaliado semanalmente e o a ingestão alimentar e hídrica diariamente. Foi utilizado o t-test de Student’s para amostras independentes. Resultados: não houve diferença significante entre os grupos para glicose, HDL-col e TG na medida basal. Após 15 semanas de intervenção, grupo HFD mostrou um aumento dos níveis de TG (p=0,01) e glicose (p=0,01) e diminuição de HDL-col (p=0,009) quando comparados com CG. Grupo HFD apresentou maior TAV (p=0,005) e peso do fígado (p=0,01). CG mostrou um aumento de ingestão alimentar e hídrica (p<0,001 e p<0,001 respectivamente) enquanto que o consumo energético foi maior no grupo HFD (p<0,001). Não foi encontrada diferença no peso das glândulas adrenais (p=0,07) e peso ponderal (p=0,63). Conclusão: os animais submetidos à dieta hiperlipídica apresentaram alterações metabólicas apesar da manutenção do peso corporal. Não foi encontrada correlação entre peso corporal e quantidade de TAV, sugerindo que o peso corporal não é preditor para quantidade de gordura corporal e que a composição da dieta influi diretamente nos marcadores de SM. / Background and Aim: Shift workers, particularly night workers, more frequently present metabolic changes when compared to day workers suggesting a predisposition for cardiovascular disease. These changes are known as Metabolic Syndrome (MS). Therefore, to increase understanding of the consequences of a high-fat diet it is important to standardize a diet for experimental animals that mimics the shift workers’ diet and its effects. Methods and Results: experimental study with 20 Wistar rats of which 10 were control group (CG) and 10 high-fat diet group (HFD). Three of five criteria for MS diagnosis from NCEP-ATP III were assessed. The amount of visceral adipose tissue was determined (VAT). Body weight was assessed weekly and food and water intake were measured daily. Student’s t-test for independent samples was used. The groups were similar at baseline. After fifteen weeks of intervention, HFD group showed an increase in serum TG (p=0.01) and glucose (p=0.01) levels and a decrease in HDL (p=0.009) compared to CG. HFD showed increased VAT (p=0.005) and liver weight (p=0.01). Food intake and water intake were higher in CG (p<0.001 and p<0.001 respectively) while energy intake was increased in HFD (p<0.001). No difference was found in adrenal glands weight (p=0.07) and body weight (p=0.63). Conclusion: Animals submitted to HFD present significant metabolic alterations in spite of the maintenance of body weight. Body weight is not a predictive factor for the amount of VAT and that the quality of diet composition direct influences MS markers.
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Alterações metabólicas decorrentes de dieta hiperlipídica em modelo animal não resistente à insulinaRamalho, Leticia January 2011 (has links)
Objetivo: Sabe-se que trabalhadores noturnos tem preferência por lanches com maior concentração de gordura saturada. Trabalhadores de turno, particularmente trabalhadores noturnos, apresentam mais frequentemente hipertrigliceridemia e hiperglicemia, bem como menores níveis de HDL-colesterol quando comparados a trabalhadores diurnos, devido a alterações circadianas e estilo de vida, sugerindo uma predisposição para o desenvolvimento de doenças cardiovasculares. Estas alterações são conhecidas como Síndrome Metabólica (SM). Portanto, para entender as conseqüências de uma dieta hiperlipídica é importante a padronização de dietas para modelos animais que mimetizem a alimentação do trabalhador de turno. Materiais e Método: estudo experimental com 20 ratos Wistar dos quais 10 eram controle (CG) e 10 submetidos à dieta hiperlipídica (HFD). Utilizaram-se três dos cinco critérios do NCEP-ATP III para diagnóstico de SM - glicose, triglicerídeos (TG) e HDL-col. A quantidade de tecido adiposo visceral (TAV) foi avaliada bem como o peso do fígado e das glândulas adrenais. O peso ponderal foi avaliado semanalmente e o a ingestão alimentar e hídrica diariamente. Foi utilizado o t-test de Student’s para amostras independentes. Resultados: não houve diferença significante entre os grupos para glicose, HDL-col e TG na medida basal. Após 15 semanas de intervenção, grupo HFD mostrou um aumento dos níveis de TG (p=0,01) e glicose (p=0,01) e diminuição de HDL-col (p=0,009) quando comparados com CG. Grupo HFD apresentou maior TAV (p=0,005) e peso do fígado (p=0,01). CG mostrou um aumento de ingestão alimentar e hídrica (p<0,001 e p<0,001 respectivamente) enquanto que o consumo energético foi maior no grupo HFD (p<0,001). Não foi encontrada diferença no peso das glândulas adrenais (p=0,07) e peso ponderal (p=0,63). Conclusão: os animais submetidos à dieta hiperlipídica apresentaram alterações metabólicas apesar da manutenção do peso corporal. Não foi encontrada correlação entre peso corporal e quantidade de TAV, sugerindo que o peso corporal não é preditor para quantidade de gordura corporal e que a composição da dieta influi diretamente nos marcadores de SM. / Background and Aim: Shift workers, particularly night workers, more frequently present metabolic changes when compared to day workers suggesting a predisposition for cardiovascular disease. These changes are known as Metabolic Syndrome (MS). Therefore, to increase understanding of the consequences of a high-fat diet it is important to standardize a diet for experimental animals that mimics the shift workers’ diet and its effects. Methods and Results: experimental study with 20 Wistar rats of which 10 were control group (CG) and 10 high-fat diet group (HFD). Three of five criteria for MS diagnosis from NCEP-ATP III were assessed. The amount of visceral adipose tissue was determined (VAT). Body weight was assessed weekly and food and water intake were measured daily. Student’s t-test for independent samples was used. The groups were similar at baseline. After fifteen weeks of intervention, HFD group showed an increase in serum TG (p=0.01) and glucose (p=0.01) levels and a decrease in HDL (p=0.009) compared to CG. HFD showed increased VAT (p=0.005) and liver weight (p=0.01). Food intake and water intake were higher in CG (p<0.001 and p<0.001 respectively) while energy intake was increased in HFD (p<0.001). No difference was found in adrenal glands weight (p=0.07) and body weight (p=0.63). Conclusion: Animals submitted to HFD present significant metabolic alterations in spite of the maintenance of body weight. Body weight is not a predictive factor for the amount of VAT and that the quality of diet composition direct influences MS markers.
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