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Molecular mechanisms linking adipose tissue dysfunction and atherosclerotic complications
Kratochvílová, Helena ; Haluzík, Martin (advisor) ; Bužga, Marek (referee) ; Cibičková, Ľubica (referee)
Obesity and its associated comorbidities increase the risk of mortality. The development of subclinical inflammation associated with obesity also plays a significant role in this. In our work, we focused on changes in the endocrine and mitochondrial function of adipose tissue and their relationship to cardiovascular complications. The first part of the thesis focuses on determining the expression of mitochondrial and endoplasmic reticulum genes in epicardial and subcutaneous adipose tissue, intercostal muscle or right myocardial atrium in patients with atherosclerotic coronary artery disease. Patients with coronary artery disease had reduced expression of several mitochondrial chain genes in epicardial adipose tissue compared to subcutaneous adipose tissue and other tissues, while no change in endoplasmic reticulum gene expression in the above-mentioned tissues has been demonstrated. Based on decreased mitochondrial gene expression in patients with coronary artery disease, we conclude that mitochondrial dysfunction of epicardial adipose tissue may contribute to the development of coronary atherosclerosis. The second part of the thesis is focused on neudesin, new potentional regulator of energy metabolism, in obese patients with type 2 diabetes mellitus (T2DM), who underwent various weight reduction...
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Characterization of energy metabolism of murine models of obesity
Irodenko, Ilariia ; Bardová, Kristina (advisor) ; Šilhavý, Jan (referee)
Energy metabolism involves processes of energy intake and energy expenditure, including storage of excessive energy in a form of lipids. White adipose tissue stores energy and plays an important role in maintenance of energy homeostasis. Animals obtain energy by oxidation of substrates from diet. Indirect calorimetry is a method for assessment of energy expenditure based on a measurement of oxygen consumption and carbon dioxide production. The VCO2/VO2 ratio (Respiratory Quotient) indicates oxidation of specific metabolic substrates. Metabolic flexibility is the ability of an organism to match substrate oxidation to its availability. The decrease of a metabolic flexibility is linked to inability to adapt to available substrate and with excessive lipid storage in the body. In this thesis we evaluated correlation between the metabolic flexibility defined by indirect calorimetry and the adipose tissue metabolism in two strains of mice, C57Bl/6J and AJ, that differ in their propensity to diet-induced obesity. Increased whole-body metabolic flexibility in A/J mice was connected to higher ability of adipose tissue to release and uptake lipids. The study of reaction to high-fat diet enables us to distinguish "metabolically healthy" and "metabolically unhealthy" adipose tissue. The knowlegde of these...
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Maturation of AMPK in skeletal muscle during early postnatal development
Hansíková, Jana ; Janovská, Petra (advisor) ; Kalous, Martin (referee)
AMP-activated protein kinase (AMPK) is an important metabolic sensor in eukaryotic organisms and it plays an important role in regulating energy homeostasis, at both the cells and the whole organism. AMPK controls glucose and lipid metabolism by direct stimulation of enzymes or by long term stimulation of the gene expression of energy metabolism. Skeletal muscles significantly contribute to the total body weight and metabolic rate and to the maintenance of glucose homeostasis. Due to the ability of the muscle to increase energy expenditure to 95% of whole-body energy expenditure, could be the proper development and programming of metabolism in the early postnatal period crucial for the further development of the organism in adulthood. Early postnatal development leads to substantial changes in energy requirements of the body and this suggests the significant involvement of AMPK in this period. The aim of this thesis was to study the activity and expression of isoforms of the catalytic subunit of AMPK in skeletal muscle during early postnatal development of both mouse strains A/J and C57BL/6 that differ in the development of diet-induced obesity. The next task was to analyze the expression of selected genes involved in energy metabolism - GLUT4, PGC-1α and UCP3 that AMPK regulates. It was found that the...
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Characterization of energy metabolism of murine models of obesity
Irodenko, Ilariia ; Bardová, Kristina (advisor) ; Šilhavý, Jan (referee)
Energy metabolism involves processes of energy intake and energy expenditure, including storage of excessive energy in a form of lipids. White adipose tissue stores energy and plays an important role in maintenance of energy homeostasis. Animals obtain energy by oxidation of substrates from diet. Indirect calorimetry is a method for assessment of energy expenditure based on a measurement of oxygen consumption and carbon dioxide production. The VCO2/VO2 ratio (Respiratory Quotient) indicates oxidation of specific metabolic substrates. Metabolic flexibility is the ability of an organism to match substrate oxidation to its availability. The decrease of a metabolic flexibility is linked to inability to adapt to available substrate and with excessive lipid storage in the body. In this thesis we evaluated correlation between the metabolic flexibility defined by indirect calorimetry and the adipose tissue metabolism in two strains of mice, C57Bl/6J and AJ, that differ in their propensity to diet-induced obesity. Increased whole-body metabolic flexibility in A/J mice was connected to higher ability of adipose tissue to release and uptake lipids. The study of reaction to high-fat diet enables us to distinguish "metabolically healthy" and "metabolically unhealthy" adipose tissue. The knowlegde of these...
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Structural composition and functional properties of mitochondrial FoF1 ATP synthase on models of specific subunits deficiencies
Efimova, Iuliia ; Mráček, Tomáš (advisor) ; Kalous, Martin (referee)
Mitochondrial ATP synthase represents the final complex of oxidative phosphorylation (OXPHOS) system located in the inner mitochondrial membrane. Its primary role is to utilize mitochondrial membrane potential (Δψm) generated by respiratory chain complexes to produce energy in the form of ATP. Mammalian ATP synthase comprises of 17 different subunits organized into membranous Fo and matrix-oriented F1 domains. Defects of complex V and their manifestation have been studied on mitochondrial, cellular, tissue and organism levels using different models, including human cell lines and cell lines derived from patient tissues. In many cases mitochondrial diseases display threshold behaviour, when genetic defect is phenotypically manifested only bellow certain threshold in particular enzyme complex activity and/or content. This work was aimed at elucidation of functional consequences of ATP synthase deficiency in HEK293 cell lines with suppressed gene expression of γ, δ or ε subunits of ATP synthase central stalk. We have analysed range of clones with respective subunits knockdown and found varying decrease in assembled ATP synthase content, which was mirrored by the decrease in individual ATP synthase subunits. The only exception was subunit Fo-c, whose levels remained unchanged or even increased. ATP...
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Maturation of AMPK in skeletal muscle during early postnatal development
Hansíková, Jana ; Janovská, Petra (advisor) ; Kalous, Martin (referee)
AMP-activated protein kinase (AMPK) is an important metabolic sensor in eukaryotic organisms and it plays an important role in regulating energy homeostasis, at both the cells and the whole organism. AMPK controls glucose and lipid metabolism by direct stimulation of enzymes or by long term stimulation of the gene expression of energy metabolism. Skeletal muscles significantly contribute to the total body weight and metabolic rate and to the maintenance of glucose homeostasis. Due to the ability of the muscle to increase energy expenditure to 95% of whole-body energy expenditure, could be the proper development and programming of metabolism in the early postnatal period crucial for the further development of the organism in adulthood. Early postnatal development leads to substantial changes in energy requirements of the body and this suggests the significant involvement of AMPK in this period. The aim of this thesis was to study the activity and expression of isoforms of the catalytic subunit of AMPK in skeletal muscle during early postnatal development of both mouse strains A/J and C57BL/6 that differ in the development of diet-induced obesity. The next task was to analyze the expression of selected genes involved in energy metabolism - GLUT4, PGC-1α and UCP3 that AMPK regulates. It was found that the...
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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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Importance of AMP-activated protein kinase in the regulation of energy metabolism of mammals
Hansíková, Jana ; Janovská, Petra (advisor) ; Žurmanová, Jitka (referee)
Enzyme AMP-activated protein kinase (AMPK) is a serin/threonin protein kinase, its main role is in energy regulation at both on the cellular and whole body levels. As a stress sensor controls the oxidation of fatty acid, transport and uptake of glucose uptake into cell, gluconeogenesis and other metabolic pathway in tissue such as liver, skeletal muscle and adipose tissue including hypothalamic central regulation of food intake and energy expenditure. Regulation of AMPK on whole-body level is coordinated by a variety of hormones (adipokines) secreted by adipose tissue. Leptin is one of key adipokines associated with the efect of AMPK . Effects of leptin are linked to both programming the metabolism in the perinatal period and with important regulations in adult metabolism. Data about development of AMPK in the hypothalamus and peripheral tissues in the perinatal period are still rare. Considering to the key role of AMPK in mediation of central regulation of leptin in the hypothalamus and metabolic effects of leptin in muscle, further research to expand knowledge in this area is required.
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