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Association of fatty acid composition in serum and / or adipose tissue lipids with lipid and carbohydrate metabolism in obese subjects of different age categories
Metelcová, Tereza ; Kunešová, Marie (advisor) ; Müllerová, Dana (referee) ; Štich, Vladimír (referee)
Obesity is a chronic disease that is caused by many factors. Excessive adipose tissue is involved in the development of metabolic and cardiovascular diseases. Prevention of cardiometabolic risks includes lifestyle arrangement, including an increased intake of omega 3 polyunsaturated fatty acids (PUFA). In additional to lifestyle factors, genetics factors also significantly contribute to influencing carbohydrate and lipid metabolism. In study A, we monitored 670 subjects (336 girls and 334 boys). Single-nucleotide polymorphisms (SNPs) in the FADS1 gene (rs174546, rs174537) was assessed using real-time PCR and then we determined the spectrum of fatty acids (FAs). The results show that SNPs in the FADS1 affect the efficiency of synthesis by affecting the activity of delta 5 desaturase. Abnormal FAs composition can affect cardiometabolic health. Study B examined a cohort of 215 individuals (131 women and 84 men) who participated in both rounds of the Childhood Obesity Prevalence And Treatment (COPAT) project. The individuals were divided into two groups: BMI≤25 kg/mš and BMI≥25 kg/mš. This model was evaluated regardless of sex because the variable sex did not correlate significantly with the variable weight status. The percentage of adipose tissue was used as the second parameter. The second parameter...
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Effect of ectopic synthesis of mitochondrial uncoupling protein 1 in white adipose tissue on whole-body metabolism in mice
Janovská, Petra ; Kopecký, Jan (advisor) ; Drahota, Zdeněk (referee) ; Kalous, Martin (referee)
The prevention and treatment of obesity is a major problem of health care systems in affluent societies. Metabolism of adipose tissue belongs to the therapeutical targets, since accumulation of adipose tissue is the basis of obesity development. Experiments using transgenic mice with ectopic expression of brown- fat uncoupling protein 1 (UCP1) in white adipose tissue (WAT), verified a concept that obesity could be ameliorated by increasing energy expenditure in WAT. The goal of the experiments of this PhD Thesis was to characterize in detail the phenotype of this unique animal model of obesity resistance. We have shown that mitochondrial uncoupling in WAT resulted in increased oxidation of fatty acids (FA), in face of decreased lipogenesis and induced mitochondrial biogenesis in this tissue. In further studies, we aimed to modulate propensity to obesity be increasing FA oxidation in WAT in response to physiological stimuli. This could be accomplished in response to the combination treatment using n-3 polyunsaturated fatty acids (n-3 PUFA) and mild calorie restriction in mice fed high-fat diet. Synergistic induction of mitochondrial oxidative capacity and lipid catabolism in epididymal WAT was associated with suppression of low-grade inflammation of WAT, which is typical for obesity. The improvement of lipid...
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Effect of metformin on glucose tolerance in relation to fat content in diet
Kuchaříková, Petra ; Horáková, Olga (advisor) ; Škop, Vojtěch (referee)
Prevalence of obesity and associated diseases like type 2 diabetes has increased rapidly during last years. These diseases closely relate to each other. Obesity leads to insulin resistence, which directly precedes type 2 diabetes. Metformin is the most prescribed medicament for type 2 diabetic patients and insulin resistant people. It improves glucose tolerance and insulin resistance. Enzyme AMP-activated protein kinase (AMPK) is strogly involved in metformin action. The latest studies using transgenic models lacking AMPK suggest, that notable part of mechanisms involved in metformin action is independent on AMPK. n-3 polyunsaturated fatty acids (n-3 PUFA), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are abundant in sea fish, have beneficial effects on metabolism. These fatty acids lower plasma lipids and exert cardioprotective effects. n-3 PUFA also prevent development of insulin resistence and type 2 diabetes in rodents. The aim of this thesis was to characterise acute effects of metformin on glucose homeostasis, impact of short term diet intervention with diet rich in n-3 PUFA on metformin action and the role of insulin stimulated signalling pathways and AMPK. Results suggest that early effect of metformin is dose dependent and that single dose of metformin...
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The role of lipids in the pathogenesis of liver diseases.
Šmíd, Václav ; Muchová, Lucie (advisor) ; Rumlová, Michaela (referee) ; Mičuda, Stanislav (referee)
1 Abstract In this thesis I have focused on the role of lipids in the pathogenesis of liver diseases, specifically on cholestasis and non-alcoholic fatty liver disease (NAFLD). The first major aim was to clarify the changes in liver ganglioside metabolism in various types of cholestasis and to elucidate the role of heme oxygenase-1 (HMOX1) and associated oxidative stress. The second objective was to determine the effects of n-3 polyunsaturated fatty acids (n-3 PUFA) administration on NAFLD development in a rodent dietary model of NAFLD and in patients with metabolic syndrome and NAFLD. Our results suggest that increased ganglioside biosynthesis and their re-distribution might represent a general protective mechanism of hepatocytes under cholestatic conditions (both estrogen-induced and obstructive aetiology). These changes are closely related to oxidative stress and might protect hepatocytes against deleterious effect of accumulated bile acids. The lack of HMOX1 activity and subsequent oxidative stress potentiate pathological changes in the liver and resulted in tissue-specific modulation of synthesis and re-distribution of gangliosides (in vivo and in vitro). Contrary to it, HMOX1 activation has an opposite effect and may represent a general hepatoprotective mechanism. We have proven that observed changes...
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Effect of metformin on glucose tolerance in relation to fat content in diet
Kuchaříková, Petra ; Horáková, Olga (advisor) ; Škop, Vojtěch (referee)
Prevalence of obesity and associated diseases like type 2 diabetes has increased rapidly during last years. These diseases closely relate to each other. Obesity leads to insulin resistence, which directly precedes type 2 diabetes. Metformin is the most prescribed medicament for type 2 diabetic patients and insulin resistant people. It improves glucose tolerance and insulin resistance. Enzyme AMP-activated protein kinase (AMPK) is strogly involved in metformin action. The latest studies using transgenic models lacking AMPK suggest, that notable part of mechanisms involved in metformin action is independent on AMPK. n-3 polyunsaturated fatty acids (n-3 PUFA), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are abundant in sea fish, have beneficial effects on metabolism. These fatty acids lower plasma lipids and exert cardioprotective effects. n-3 PUFA also prevent development of insulin resistence and type 2 diabetes in rodents. The aim of this thesis was to characterise acute effects of metformin on glucose homeostasis, impact of short term diet intervention with diet rich in n-3 PUFA on metformin action and the role of insulin stimulated signalling pathways and AMPK. Results suggest that early effect of metformin is dose dependent and that single dose of metformin...
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Effect of ectopic synthesis of mitochondrial uncoupling protein 1 in white adipose tissue on whole-body metabolism in mice
Janovská, Petra ; Kopecký, Jan (advisor) ; Drahota, Zdeněk (referee) ; Kalous, Martin (referee)
The prevention and treatment of obesity is a major problem of health care systems in affluent societies. Metabolism of adipose tissue belongs to the therapeutical targets, since accumulation of adipose tissue is the basis of obesity development. Experiments using transgenic mice with ectopic expression of brown- fat uncoupling protein 1 (UCP1) in white adipose tissue (WAT), verified a concept that obesity could be ameliorated by increasing energy expenditure in WAT. The goal of the experiments of this PhD Thesis was to characterize in detail the phenotype of this unique animal model of obesity resistance. We have shown that mitochondrial uncoupling in WAT resulted in increased oxidation of fatty acids (FA), in face of decreased lipogenesis and induced mitochondrial biogenesis in this tissue. In further studies, we aimed to modulate propensity to obesity be increasing FA oxidation in WAT in response to physiological stimuli. This could be accomplished in response to the combination treatment using n-3 polyunsaturated fatty acids (n-3 PUFA) and mild calorie restriction in mice fed high-fat diet. Synergistic induction of mitochondrial oxidative capacity and lipid catabolism in epididymal WAT was associated with suppression of low-grade inflammation of WAT, which is typical for obesity. The improvement of lipid...
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Energetický metabolismus inbredních myších linií a jeho ovlivnění dietou
Kůs, Vladimír ; Kopecký, Jan (advisor) ; Nováková, Olga (referee) ; Mráček, Tomáš (referee)
Obesity and associated metabolic disorders, called as "metabolic syndrome", currently represent a major social and economical problem of public health. From the energy balance point of view, long-lasting energy surplus leads eventually to massive accumulation of energy stores resulting in various adverse effects on metabolism and health. General goal of the thesis was to examine these metabolic disorders at cellular and whole-body level using suitable mouse models. The main focus was on the most metabolically active tissue, namely skeletal muscle, liver and adipose tissue and on the regulatory roles of AMP-activated protein kinase (AMPK) and leptin in the energy metabolism. The whole thesis is based on four published studies. Two studies were focused on skeletal muscle. In the first study, we proved the involvement of leptin and AMPK in the metabolic response to high-fat diet-feeding. We described a mechanism of muscle non- shivering thermogenesis based on enhanced lipid catabolism, which contributes to the genetically-determined resistance of inbred A/J mice to obesity. Such mechanism was not operating in obesity-prone C57BL/6 mice. In the second study, performed using C57BL/6 mice, we have described beneficial effect of combination treatment using n-3 polyunsaturated fatty acids (n-3 PUFA) of...
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Effect of alternative feed on content of omega 3 fatty acids in fish muscles
KREJSA, Jakub
The aim of my bachelor thesis was to evaluate the effect of fish oil substitution for rapeseed oil in the feed on the fat content and fatty acid composition in the flesh of Brook trout (Salvelinus fontinalis) in the finishing feeding technology. The experiment was conducted in 2012 for the period of 135 days. The individuals of Brook trout were divided into four groups. The first two groups were fed with the feed containing only rapeseed or fish oil. The feeding of the remaining two groups was divided into two phases. In the first phase the fish oil was partly replaced by the rapeseed oil. In the second phase the fish oil was replaced by the feed which contained fish oil only. It was proved that a half replacement of the fish oil with the rapeseed oil does not influence the content of fat in the flesh of Brook trout. We observed that the fish had the higher content of MUFA and n-6 PUFA and lower content of n-3 PUFA, DHA, EPA and n-3/n-6 with increasing period where the feed with rapeseed oil was served. Following application of the finishing feeding technology with the use of feed with fish oil had the opposite effects. Furthermore, the dilution model was proved to be highly reliable for the prediction of the fatty acids composition. Based on these findings, it is possible to predict changes of fatty acid composition in the flesh of Brook trout as well as to predict how long is needed to apply finishing feeding to reach required content of EPA+DHA or n-3 HUFA.
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