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Characterization of epicardial, pericardial, and perivascular adipose tissue in humans and mice
Rybová, Aneta ; Bardová, Kristina (advisor) ; Kuneš, Jaroslav (referee)
Heart-associated adipose tissue plays an important role in the physiology of the cardiovascular system. Not only does it serve as a protection against mechanical and thermal stress, but it also provides energy for the cardiomyocytes. On the other hand, it can also act as a tissue that promotes a proinflammatory state around the heart, which can result in the development of cardiovascular diseases. Information from the study of epicardial, perivascular or paracardial and other adipose tissue surrounding the heart and large vessels may be used in the prevention of pathological conditions of the heart that are associated with the presence of this adipose tissue.
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Effects of stable analogs of anorexigenic neuropeptides in models of metabolic syndrome
Mráziková, Lucia ; Maletínská, Lenka (advisor) ; Kříž, Jan (referee) ; Bardová, Kristina (referee)
Obesity is a worldwide health problem and an effective treatment is still scarce. Anorexigenic neuropeptides, such as prolactin-releasing peptide (PrRP), have a potential for the treatment of obesity and its complications, but in their natural form they have several limitations such as poor bioavailability, low stability and inability to cross the blood-brain barrier after peripheral administration. Recently we have designed lipidized analogs of PrRP. Lipidization makes this peptide more stable and able to act centrally after peripheral administration. The aim of this study was to investigate the chronic effect of PrRP palmitoylated at position 11 (palm11 -PrRP31) on obesity and obesity-related metabolic parameters and to clarify mechanisms of its action. We used three rodent models of obesity: Wistar Kyoto (WKY) rats with high-fat diet-induced obesity (DIO) having intact leptin and leptin receptor as well as rodents with disrupted leptin function: leptin deficient ob/ob mice and fa/fa rats with a disturbed leptin signaling. Consumption of a high-fat diet in DIO WKY rats increased their body weight, caused strong glucose intolerance and increased liver mRNA expression of enzymes of de novo lipogenesis. Palm11 -PrRP31 treatment significantly decreased cumulative food intake, body weight, plasma...
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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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Adipose tissue metabolism and genetically modified murine models
Irodenko, Ilariia ; Bardová, Kristina (advisor) ; Železná, Blanka (referee)
Adipose tissue plays an important role in energy and glucose homeostasis. Adipose tissue metabolism includes lipolysis and lipogenesis processes which control lipid mobilization, storage and distribution in the body. In addition to that adipose tissue is recognized as an endocrine organ which generates cytokines and adipokines for communication with other organs and tissues. The major process of lipogenesis is triacylglycerol synthesis which comprises such enzymes as monoacylglycerol acyltransferase and diglyceride acyltransferase for triacylglycerol storage in a form of lipid droplets. The other way around main enzymes of lipolysis adipose triglyceride lipase and hormone-sensitive lipase produce sufficient amount of energy for other tissues. Lipid combustion in brown adipose tissue produces heat in the body through the function of uncoupling protein 1. Signaling pathways of lipolysis and thermogenesis comprise adrenergic receptors. Study of thermogenic function of uncoupling protein and adipose tissue metabolism can be useful for the treatment of obesity and metabolic disorders.
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The role of energy metabolism in cardioprotection induced by the adaptation to chronic hypoxia
Kolář, David ; Žurmanová, Jitka (advisor) ; Adamcová, Michaela (referee) ; Bardová, Kristina (referee)
Cardiac energy metabolism is the one of the most complex system in the body. To sustain life, but also to respond quickly to any sudden changes (e.g. running, emotional stress), the heart has developed a unique ability and has become a metabolic "omnivore". At physiological conditions, long chain fatty acids (LCFAs) present the major energetic source for the adult myocardium. However, the cardiac energy metabolism may be compromised during pathophysiological states. One of the most dangerous is, undoubtedly, ischaemia-reperfusion injury with its acute form, myocardial infarction. However, the adaptation to chronic hypoxia has been known for decades for its cardioprotective effect against I/R. Changes of cardiac energy metabolism induced by the adaptation have not been fully explored and the system conceals still too many secrets. This thesis has aimed to determine how adaptation to chronic hypoxia affects the cardiac metabolism of the rat LVs in the following set-ups: 1. The effect of chronic normobaric hypoxia (CNH; 3 weeks, 5500m) during a brief I/R protocol in vitro on the protein kinase B/hexokinase (Akt/HK) pathway, including the expression and phosphorylation of Akt, the expression and localization of HK, the expression of mitochondrial creatine kinase (mtCKS), and the level of Bcl-2 family...
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Role of uncoupling protein UCP2 in immune cells
Fikarová, Natálie ; Krulová, Magdaléna (advisor) ; Bardová, Kristina (referee)
UCP2 is one of four discovered homologues of a well-known uncoupling protein UCP1 implicated in non-shivering thermogenesis. In contrast to UCP1, this particular homologue is ubiquitously expressed in many human tissues, where it performs a broader range of functions including uncoupling and specific transport of ions and metabolites. This work characterises UCP2, focusing on its activity in the cells of innate and adaptive immunity. To conclude, this work summarises the role of UCP2 in several diseases, such as Type 1 diabetes mellitus, Alzheimer's and Parkinson's disease and ulcerative colitis. Emphasis is put on the possible utilisation of this protein in the treatment of the above-mentioned diseases. Keywords: immune cells, uncoupling proteins, UCP2
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The role of NADPH oxidase in architecture and function of β cells and Langerhans Islets
Tučková, Štěpánka ; Plecitá, Lydie (advisor) ; Bardová, Kristina (referee)
Local production of reactive oxygen species (ROS) and changes in the redox environment influence the metabolism and function of β cells of the Langerhans islets (LO). Changing the ratio between NAD(P)H / NAD(P)+ redox partners significantly affects sensitive proteins and ROS production. ROS are able to reversibly modify some amino acid residues (eg Cys, Met) of antioxidant enzymes and their interaction partners. Such a signaling cascade allows the transmission of a signal over longer distances and can also interfere with the influence of gene expression. The unique enzyme NADPH oxidase 4 (NOX4) is present on membranes within β cells and constitutively produces H2O2 depending on the presence of NAD(P)H. After glucose stimulation, both NAD(P)H and Nox4 mRNA levels increase. As previously observed in our laboratory, C57BL/6J mice with a specific Nox4 deletion in β cells have a disrupted biphasic insulin release and exhibit insulin resistance in fat and muscle tissue. We found that the absence of NOX4 in C57BL/6J mice affects LO architecture. Wildtype (WT) mice on a normal, predominantly carbohydrate diet (ND) have the majority of small LO with an area of up to 5 000 μm2 (measured on histological sections). High-fat diet (HFD) feeding of WT for 8 weeks leads to the development of diabetic phenotype and...
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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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The role of energy metabolism in cardioprotection induced by the adaptation to chronic hypoxia
Kolář, David ; Žurmanová, Jitka (advisor) ; Adamcová, Michaela (referee) ; Bardová, Kristina (referee)
Cardiac energy metabolism is the one of the most complex system in the body. To sustain life, but also to respond quickly to any sudden changes (e.g. running, emotional stress), the heart has developed a unique ability and has become a metabolic "omnivore". At physiological conditions, long chain fatty acids (LCFAs) present the major energetic source for the adult myocardium. However, the cardiac energy metabolism may be compromised during pathophysiological states. One of the most dangerous is, undoubtedly, ischaemia-reperfusion injury with its acute form, myocardial infarction. However, the adaptation to chronic hypoxia has been known for decades for its cardioprotective effect against I/R. Changes of cardiac energy metabolism induced by the adaptation have not been fully explored and the system conceals still too many secrets. This thesis has aimed to determine how adaptation to chronic hypoxia affects the cardiac metabolism of the rat LVs in the following set-ups: 1. The effect of chronic normobaric hypoxia (CNH; 3 weeks, 5500m) during a brief I/R protocol in vitro on the protein kinase B/hexokinase (Akt/HK) pathway, including the expression and phosphorylation of Akt, the expression and localization of HK, the expression of mitochondrial creatine kinase (mtCKS), and the level of Bcl-2 family...
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Molecular mechanism of insulin release
Tučková, Štěpánka ; Plecitá, Lydie (advisor) ; Bardová, Kristina (referee)
Insulin reduces glucose levels in blood and has impact on metabolism, cell- cycle and proliferation of target body cells. Its secretion from pancreatic β cells is induced right after food consumption, utilization in digestion system and nutrient elevation in blood circulation. Under physiological conditions molecular mechanisms include simultaneous effect of glucose, fatty acids, amino acids, ions, reactive oxygen species and neural and humoral system. The primary inducer is glucose, which is necessary also for insulin gene expression. Glucose modulates the fate of other nutrients, which enhance glucose stimulated insulin secretion. In general, glucose decreases fatty acid beta oxidation and increases the level of effector lipid intermediates in cytoplasm. The key processes within insulin release pathways are the Krebs cycle, pyruvate cycling and glycerole-3-phosphate/free fatty acids cycle. Moreover, endocrine signaling molecules, hormones and nervous system regulate insulin secretion through their receptors on β cell membranes. Disruption of regulatory mechanisms and insulin sensitivity of peripheral tissues may lead to development of diabetes mellitus.
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