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Energy metabolism of inbred mouse strains and its modulation by diet
Kůs, Vladimír
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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Energy metabolism of inbred mouse strains and its modulation by diet
Kůs, Vladimír
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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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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Endogenous steroid dehydroepiandrosterone and its role in modulation of local metabolism of glucocorticoids
Imrichová, Terezie ; Pácha, Jiří (advisor) ; Kůs, Vladimír (referee)
The anti-glucocorticoid effect of dehydroepiandrosterone (DHEA) have been known for many years. However, its molecular basis have not been elucidated yet. The results of certain experiments suggest that not DHEA but its 7-oxygenated metabolites 7-OH-DHEA, 7-OH-DHEA a 7-oxo-DHEA are the antiglucocorticoid molecules. Various hypothesis about how these steroids exert their antiglucocorticoid action have been tested during the last several years. Some of them were reliably disproved (e.g. the competitive inhibition of glucocorticoid receptors), others were validated (e.g. the DHEA-mediated change in expression of certain enzymes participating in glucocorticoid metabolism), and yet others are still being considered. Nevertheless, clarifying the nature of the anti-glucocorticoid effect of DHEA or its metabolites is crucial for its possible use as a therapeutic drug.
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