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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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Effect of stable prolactin-releasing peptide analog in rat model of obesity
Pospíšilová, Kateřina ; Maletínská, Lenka (advisor) ; Bardová, Kristina (referee)
Obesity is a serious worldwide problem of modern society. Current state is at epidemic level not just in the developed world. It is no more "western disease" or "disease of affluence" as obesity used to be called. Determination of mechanisms that regulate energy balance in the human organism is necessary for further development of obesity drugs. Prolactin-releasing peptide (PrRP) is anorexigenic (food intake lowering) neuropeptide, which acts centrally in hypothalamus. Lipidized analogs of PrRP are promising tools in obesity and type-two diabetes mellitus treatment. This work is focused on impact of palmitoylated analog of prolactin-releasing peptide (palm11 -PrRP31) in a diet induced rat model of obesity after chronical administration. Body weight and cumulative food intake was monitored during the experiment. Administration of palm11 -PrRP31 markedly lowered food intake which caused decrease of body weight compared to obese control group on high-fat diet. This reduction correlated with significantly lower amount of intraperitoneal fat compared to group on high fat-diet. Also, high-fat diet worsened studied metabolic parameters including glucose tolerance. Palm11 -PrRP31 lowered leptin plasma level and improved glucose tolerance both compared to the high-fat fed. Therefore, palm11 -PrRP31 is...
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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 demethylase FTO and adipokines in the heart: effect of chronic hypoxia
Benák, Daniel ; Hlaváčková, Markéta (advisor) ; Bardová, Kristina (referee)
Adaptace na chronickou hypoxii zvyšuje toleranci srdce k ischemicko-reperfuznímu poškození. Tato adaptace je umožněna řadou fyziologických změn na buněčné úrovni. Jednou z nich je změna v buněčném energetickém metabolismu. Tento proces může být regulován proteinem FTO (z angl. fat mass and obesity associated), demetylázou epigeneticky regulující buněčnou syntézu proteinů. Srdeční metabolismus může být také modulován adipokiny leptinem a adiponektinem. Cílem tohoto projektu bylo proto studovat roli FTO a adipokinů v chronicky hypoxickém srdci. Dospělí samci potkanů kmene Sprague Dawley byli adaptováni na dva modely kontinuální normobarické hypoxie (CNH; 12 % O2 a 10 % O2; 3 týdny). CNH (10 % O2) redukovala u těchto zvířat rozsah infarktu myokardu o 20 %. CNH (12 % O2) nebyla kardioprotektivní. Hladina proteinu FTO byla měřena v tkáni levých (LV) a pravých (RV) komor, stejně jako v játrech a koncovém mozku hypoxických i normoxických zvířat. Za normoxie je hladina FTO v RV o 50 % vyšší než v LV. Ve vysoce metabolicky aktivních tkáních jater a koncového mozku jsou pak hladiny FTO vyšší dokonce 6krát a 11krát. CNH (12 % O2) vedla k signifikantnímu nárůstu hladiny proteinu FTO v srdci. Jednalo se o 21% nárůst v LV a 27% v RV. Hladiny v játrech a koncových mozcích nebyly CNH ovlivněny. Silnější CNH (10 % O2)...
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Adipose tissue functional changes during postnatal development and impact of high-fat diet feeding on adipose and liver tissue
Hájková, Simona ; Bardová, Kristina (advisor) ; Hlaváčková, Markéta (referee)
Caloric intake increased over a long period of time may induce the development of obesity, causing so-called low-grade inflammation. The organism responses to the inflammation by the activation and production of cellular components of the immune system, such as macrophages or proinflammatory cytokines. The adipose tissue itself is involved in the production of bioactive molecules, including leptin and adiponectin. Increased concentration of proinflammatory cytokines can lead to a dysfunction of important metabolic pathways and impair organ's function. For the purpose of closer knowledge of the etiology of obesity and its metabolic complications, inbred strains of mice with different genetic backround are most commonly used. We aimed to define the impact of high-fat diet (HFD) on adipose and liver tissue of C57BL/6J and A/J murine strains with a different susceptibility to diet-induced obesity. We focused on description of morphological and functional changes of adipose tissue and on the evaluation of plasma leptin and adiponectin levels of mice in the early postnatal development. Next, we measured the expression of leptin mRNA in four tissues. In this study we described how the increased caloric intake leads to increased triacylglycerides (TAG) storage in the liver and to a higher inflammatory...
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Energy Metabolism in Obesity: Metabolic Flexibility and Dietary Fat
Bardová, Kristina ; Kopecký, Jan (advisor) ; Drahota, Zdeněk (referee) ; Žurmanová, Jitka (referee)
Abstract Adipose tissue is an important homeostatic tissue within the body. It not only buffers FA availability in the organism, but also releases important autocrine, paracrine or endocrine factors influencing energy metabolism. The biology of adipose tissue is closely related and underlies whole-body metabolic consequences of obesity, such as type II. diabetes. Obesity and type II. diabetes causes and maybe are caused by metabolic inflexibility, the inability of organism to adapt fuel oxidation to fuel availability. The intersection of adipose tissue biology, obesity and its metabolic consequences and theory of metabolic flexibility is discussed in this PhD. thesis. Five articles dealing with above mentioned topics are included. The general goal of this study was to compare several approaches for metabolic flexibility assessment with respect to overall energy homeostasis. The specific goals, delineated by included articles, were (i) to evaluate the influence of n-3 long chain fatty acids (n-3 LC-PUFA), rosiglitazone, and their combination, on metabolic flexibility at a whole-body and cellular level; (ii) to evaluate impact of high-fat feeding on metabolic flexibility of male and female mice; (iii) to evaluate the impact of chenodeoxycholic acid (CDCA)...
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The role of immune system in development of obesity and derived metabolic complications
Jindrová, Simona ; Bardová, Kristina (advisor) ; Cinkajzlová, Anna (referee)
Obesity is a chronic disease caused by an imbalance between energy intake and expenditure. Important source of energy is the body fat, stored in adipose tissue cells in the form of triacylglycerols. The adipose tissue does not only store triacylglycerols but also functions as an endocrine organ with the ability to secrete cytokines and adipokines - the molecules, participating in series of the metabolic proceses. The consequence of high-fat diet feeding is the growth of adipose cells and altered production od adipokines and cytokines. Majority of them have proinflammatory functions. Consequently inflammation of adipose tissue is increased as well as the activation of components of immune system, especially macrophages. The interplay between these and other aspects, including hight free fatty acid plasma levels, also associated with metabolic disorders caused by obesity, is connected with the development of insulin resistance, that means state, when the tissues are nonsensitive to insulin. Key words: obesity, adipokines, cytokines, immune system, adipose tissue, insulin resistance
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Characterization of obesogenic diet effect on adipose depots in mice C57BL/6J
Matějková, Mirka ; Bardová, Kristina (advisor) ; Lacinová, Zdeňka (referee)
Obesity is closely related to insulin resistance development, ectopic fat accumulation in the liver and skeletal muscles, liver steatosis and type 2 diabetes mellitus. Adipose tissue of obese subjects produces increased quantity of adipokines, which are involved in development of insulin resistance, and in the same time macrophages causing low-grade inflammation are infiltrating into adipose tissue. Long-chain polyunsaturated fatty acids of the n-3 series have beneficial effects on adipose tissue inflammation and lipid and carbohydrate metabolic pathways in organism. There is lot of research ongoing on laboratory animals on negative consequences of obesity and possible improvement. Obesity is induced by diet with high fat content and the consequences are evaluated. I have analysed the influence of different high fat diets and a diet with long-chain polyunsaturated fatty acids of the n-3 series on homogeneity of adipose depots in the cell size and the level of inflammation. I observed gradual development of obesity due to administration of high fat diet to laboratory animals. Methods: Intraperitoneal glucose tolerance test (IPGTT), oral glucose tolerance test (OGTT), assessment of lipid metabolites in blood, assessment of triacylglycerols in the liver and in the adipose tissue, assessment of DNA in...
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