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Regulation of immunometabolism in white adipose tissue
Gazdová, Tatiana ; Horáková, Olga (advisor) ; Beňová, Andrea (referee)
High-fat diet promotes the development of diet-induced obesity, which leads to further complications such as insulin resistance and type II diabetes. The underlying cause for development of obesity associated pathologies is disruption of adipose tissue homeostasis. Excessive lipid accumulation and rapid white adipose tissue expansion stimulate infiltration, proliferation, and activation of immune cells involved in inflammation propagation. Immune cells within white adipose tissue have the ability to modulate adipocyte function as well as whole-body metabolism. These interactions and function modulations are the core topics of immunometabolism, a rapidly developing field of research focused on interpreting how immune system modulates metabolism on cellular as well as systemic level. In obesity, pro-inflammatory immune cells, for example M1 macrophages and neutrophils, outnumber homeostasis-promoting anti-inflammatory immune cells in white adipose tissue and alter the tissue environment. As a result, pro-inflammatory cytokines prevent adipocytes from adequately responding to extracellular stimuli. The resulting interactions between immune cells and adipocytes maintain inflammation and promote ectopic lipid accumulation. Experimental studies suggest that white adipose tissue inflammation can be...
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Physiologic and pathophysiologic aspects of selected endocrinopathies. Their relationship to adipose tissue matebolism and insulin resistance
Ďurovcová, Viktória ; Kršek, Michal (advisor) ; Saudek, František (referee) ; Štich, Vladimír (referee)
The pathogenesis of insulin resistance is a complex and still intensively studied issue. Endocrine and paracrine activity of the adipose tissue together with mi- tochondrial dysfunction are the most discussed potential factors included in the development of insulin resistance. In the first part of our study we examined the involvement of the adipose tissue and its secretory products in the etiopathogenesis of insulin resistance in patients with Cushing's syndrome, acromegaly and simple obesity. We focused on three important regulators of metabolic homeostasis - fibroblast growth factors 21 and 19 (FGF-21 and FGF-19) and adipocyte fatty acid binding protein (FABP-4). We found significantly elevated circulating levels of FGF-21 and FABP-4 ac- companying insulin resistance in both patients with simple obesity and patients with obesity connected to Cushing's syndrome, as compared to healthy controls. The concentrations of both substances were comparable between hypercortisolic and obese patients. This finding together with the absence of correlation be- tween the levels of FGF-21 resp. FABP-4 and cortisol suggest that the reason for elevation of their concentrations is obesity and its metabolic consequences themselves rather then the effect of hypercortisolism on FGF-21 and FABP-4 production. We found no...
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Functional genomic and pharmacogenomic analysis of metabolic syndrome aspects
Krupková, Michaela ; Šeda, Ondřej (advisor) ; Haluzík, Martin (referee) ; Polák, Jan (referee)
Metabolic syndrome is a prevalent disease characterized by concurrent manifestation of insulin resistance, obesity, dyslipidemia, hypertension and other hemodynamic and metabolic disorders. It has multifactorial type of inheritance and its resultant phenotype is determined by both environmental and genetic factors as well as their interactions. That is the main reason why comprehensive analysis of the genetic component of this syndrome is complicated in human population. Genetically designed experimental animal models are significant tools for analysis of genetic architecture of human complex conditions including the metabolic syndrome. The aim of this Thesis is utilization of functional and comparative genomic tools to uncover pathogenesis of metabolic syndrome aspects and their genetic determinants. We also studied pharmacogenetic interactions of these genetic determinants with drugs affecting particular components of the metabolic syndrome. Establishing and utilizing several genetically designed congenic rat strains, we undertook four different research projects focusing on pharmacogenetic interaction of all-trans retinoic acid and ondansetron with differential segment of rat chromosome 8, pharmacogenetic interaction of differential segment of rat chromosome 4 and dexamethasone, determining Plzf...
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Insulin Resistance and Metabolic inFlexibility : the Influence of Renin Angiotensin System Inhibition
Wohl, Petr ; Pelikánová, Terezie (advisor) ; Prázný, Martin (referee) ; Vondra, Karel (referee)
Insulin resistance (IR) is considered to be an important factor influencing the progression of atherosclerosis and is associated with higher morbidity and mortality. IR is a common feature of diabetes mellitus Type 2 and obesity. Many authors consider IR being the crucial abnormality of the metabolic syndrome which is characterized by the essential hypertension, hyperliproteinemia, visceral obesity, endothel dysfunction and many other abnormalities. Impaired insulin action (IR) is also described in diabetes mellitus Type 1, however this phenomenon has not been fully explained. The subjects of dissertation thesis was directed on the IR importance in diabetic Type 1 patients as well as on the renin angiotensin system inhibition in patients with IR and metabolic syndrome with impaired glucose homeostasis. Hyperinsulinemic euglycemic clamp is used in combination with indirect calorimetry to estimate the IR in vivo in humans. In our project we focused on a) the existence of the metabolic inflexibility phenomenon in type 1 diabetic patients b) the methodological evaluation of the hyperinsulinemic euglycemic clamp procedure in the same group c) the influence of renin angiotensin system inhibition with angiotensin II type 1 receptor inhibitor telmisartan in patients with metabolic syndrome and impaired glucose...
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Factors affecting glucose metabolism and inflammatory response in critically ill patients
Kotulák, Tomáš ; Haluzík, Martin (advisor) ; Maruna, Pavel (referee) ; Šenolt, Ladislav (referee)
Hyperglycemia in critically ill patients was considered for many years an adaptive response to stress conditions being present in both patients with and without previous history of diabetes. Hyperglycemia is caused mainly by peripheral insulin resistance induced by the factors acting counteracting insulin signalling at the postreceptor level. Furthermore, hyperglycemia itself can then increase serum levels of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-6 (Il-6) and interleukin-8 (Il- 8) and others. On the contrary, peripheral insulin resistance induced by pro- inflammatory cytokines may further potentiate hyperglycemia. White adipose tissue represents in addition to its energy storage function also a very active endocrine active organ. In addition to regulation of a number of metabolic processes it also significantly modulates the inflammatory response. In critically ill patients, adipose tissue changes its morphology, i.e. the adipocytes are shrinking and adipose tissue is abundantly infiltrated by macrophages. Paradoxically, overweight and obese critically ill patients have lower mortality than underweight, lean and morbidly obese subjects. In our studies, we selected population of the patients undergoing elective major cardiac surgery with extracorporeal...
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The analysis of mechanisms associated with beneficial metabolic effects of marine Omega-3 polyunsaturated fatty acids in different lipid forms.
Pavlišová, Jana ; Rossmeisl, Martin (advisor) ; Maletínská, Lenka (referee) ; Cahová, Monika (referee)
Obesity, one of the most serious health problems of the 21st century, often occurs as a result of an imbalance between energy intake and energy expenditure. Dietary lipids play an important role in the development of obesity, partly because they represent the richest source of energy amongst all macronutrients. It is, however, not only the amount of consumed lipids, but also the composition of fatty acids, which strongly influences health effects of a particular diet. Saturated fatty acids (SFA) are generally considered as unhealthy due to their pro-inflammatory and lipotoxic properties, while monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) represent a healthier alternative, as they are more readily oxidized and do not disrupt biochemical properties of cellular membranes. Amongst PUFA, PUFA of n-3 series (Omega-3) represent an utterly unique class of lipids that have been documented to protect against cardiovascular disease and dyslipidemia in men and improve insulin sensitivity and glucose tolerance primarily in animal models of obesity. Some molecular mechanisms of Omega-3 action have been already uncovered, such as the modification of biological membranes composition, activation of various transcription factors and membrane receptors, and their role as precursors for...
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Gestational diabetes diet
Kuchařová, Miroslava ; Krejčí, Hana (advisor) ; Anderlová, Kateřina (referee)
The Master's thesis entitled "Gestational Diabetes Diet" deals with the issue of eating habits and a lifestyle of women diagnosed with gestational diabetes mellitus during pregnancy. The theoretical part of the thesis describes the definition, causes and a mechanism of origin, consequences for mother and fetus and also deals with the diagnostic procedures and all possibilities of treatment of this disease. In this part, the diagnostic method analyzed by using the oGTT stress test and a diabetic diet - that together with other preventive measures (mainly physical aktivity) is the first choice in the treatment of pregnancy diabetes - are described in more details. The practical part of this master's thesis contains the results of a questionnaire survey in two groups of pregnant women - with already diagnosed gestational diabetes and before its diagnosis in the oGTT test. It also contains the results of the analysis of women with GDM diets. The analysis were processed by the NutriPro Expert diet program and the results are then compared with the current nutritional recommendations of the Czech Republic for pregnant and nursing women. The aim of this work was to map the eating habits and lifestyle of women with gestational diabetes and find out whether they meet current nutritional recommendations or...
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The food intake comparison of the patients with the metabolic syndrome with or without hepatosteatosis/steatohepatitis
Štičková, Zdeňka ; Macášek, Jaroslav (advisor) ; Meisnerová, Eva (referee)
The aim of this bachelor thesis is to compare the food intake in patients with metabolic syndrome, who suffer from non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). The main aim of this bachelor thesis is to find out differences in the diet of different groups of patients comprising patients with simple obesity, patients with metabolic syndrome without steatosis, patients with metabolic syndrome with steatosis and patients with metabolic syndrome complicated by steatohepatitis. This thesis is divided into two parts - theoretical and practical. The theoretical part introduces metabolic syndrome, its definition, occurrence, etiology, complications and its prevention and treatment. The topics about pathophysiology of the liver and the definition of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis are also covered. Methods: The practical part is a quantitative research in the form of questionnaires made at the 4th Internal Department at the General University Hospital in Prague. The patients met the criteria of the mentioned symptoms or diseases. The thesis compares the data from literature with the responses of the patients. We explored the question of the diet composed for example by regular intake of fermented milk products, selenium, green tea or...
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The use of magnetic resonance spectroscopy for studying glucose metabolism
Kratochvílová, Simona ; Pelikánová, Terezie (advisor) ; Štich, Vladimír (referee) ; Polák, Jan (referee)
Magnetic resonance spectroscopy (MRS) is a noninvasive technique that enables to follow metabolic processes in selected tissues in vivo. Recently the attention has been focused on metabolic mapping in target organs of insulin action to describe the pathophysiology of insulin resistance. The aim of our study was to present the practical application of ³¹P (phosphorus) MRS and ¹H (proton) MRS in metabolic studies of skeletal muscle in insulin resistant subjects and in subjects with impaired fasting glucose. The third study was aimed to evaluate the brain metabolism with ¹H MRS in healthy controls and subjects with type 1 diabetes during hyperinsulinemia. ¹H and ³¹P MRS were performed using a MR Scanner Siemens Vision operating at 1,5 Tesla. To assess the parameters of glucose metabolism and insulin action oral glucose tolerance test and hyperinsulinemic euglycemic clamp were performed. The study 1 was aimed to evaluate the skeletal muscle (m. soleus) energetic metabolism in the offspring of hypertensive parents (OH) with a higher level of insulin resistance. The concentrations of selected high energy phosphates (phosphocreatine, inorganic phosphate, adenosintriphosphate, phosphomonoesters, phosphodiesters) were evaluated with ³¹P MRS. Their amount in OH was comparable to healthy controls. However we...
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