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Role of adipose tissue in the ethiopatogenesis of insulin resistance
Polák, Jan ; Štich, Vladimír (advisor) ; Hainer, Vojtěch (referee) ; Kazdová, Ludmila (referee) ; Rossmeisl, Martin (referee)
Adipose tissue is involved in etiopathogenesis of insulin resistance and subsequent metabolic disorders including type 2 diabetes mellitus and atherosclerosis. Mechanisms responsible for this association are investigated vigorously. One of the well accepted mechanisms linking excessive accummulation of adipose tissue with a development of insulin resistance are free fatty acids, which are released into circulation after hydrolysis of triglycerides stored in adipose tissue in a process of lipolysis. Impairments in a regulation of lipolysis are described in obese patients and lead to increased plasma level of free fatty acids and to impaired mobilisation of energy stores during exercise. In this PhD thesis, regulation of lipolysis in subcutaneous abdominal adipose tissuewas investigated using microdialysis technique. In the first paper we have observed that dysregulation in catecholamine-induced lipolysis and impaired insulin action in adipose tissue can be improved by dynamic-strength training in obese men. In the second study, we have demonstrated significant involvement of newly discovered lipolytic pathway mediated by atrial natriuretic peptide in lipolysis stimulation during exercise. Adipose tissue is producing several protein substances with regulatory and endocrine functions collectively named...
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Role of adiponectin and B-type natriuretic peptide in the regulation of adipose tissue lipolysis
Wedellová, Zuzana ; Štich, Vladimír (advisor) ; Kunešová, Marie (referee) ; Cahová, Monika (referee) ; Horáková, Olga (referee)
Obesity is a most common metabolic disorder worldwide. Prevalence of obesity is consistently growing in all continents during last years. Primarily the increase of incidence of obesity in children is alarming. Obesity is linked to elevated risk of type 2 diabetes, hyperlipidemia, cardiovascular diseases, some cancers and disorders of musculoskeletal system. The cost of the treatment of diseases linked to obesity is annually increasing and obesity represents very important part of costs of health system in developed - and recently also developing - countries. This fact shows the necessity of research in the area of preventive and therapeutic procedures. The development of metabolic disturbances linked to obesity is associated with dysfunction of adipose tissue. Its two main features are: 1) altered secretion of specific substance with hormonal or paracrinne charakter (called adipokines) and 2) elevated mobilization of non- esterified fatty acids (NEMK) from adipose tissue and subsequently their increased release into the circulation (1). In our studies we paid attention to the study of lipolysis. The rate of lipolysis is the primary factor that determines the release of NEFA from adipose tissue. We focused to a role of adiponectin and natriuretic peptid type B (BNP) in the regulation of lipolysis in...
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Molecular adaptations of adipose tissue in relation to dietary treatment of obesity in human
Tencerová, Michaela ; Štich, Vladimír (advisor) ; Flachs, Pavel (referee) ; Kazdová, Ludmila (referee) ; Kunešová, Marie (referee)
The general goal of this work was to investigate the molecular adaptations of human AT in relation to DIs with respect to its secretory activity as well as cellular composition focused on macrophages population. Specifically, we studied the role of novel adipokines, such as visfatin and RBP4, related to insulin resistance and AT metabolism. Furthermore, we wanted to characterize the effect of the dietary-induced changes on the content of ATM together with metabolic amelioration. In our studies, we found that lifestyle modifications had a beneficial effect on metabolic and biochemical parameters depending on the duration and type of DI. Regarding both of the investigated adipokines, visfatin and RBP4, we revealed modifications at the transcriptional and cirulating levels during DI. However, we did not find any association with the pattern of evolution of insulin resistance. Our findings do not support a clear hypothesis on the role of these adipokines in the diet-induced improvement of insulin sensitivity and other obesity-related metabolic disturbances. In respect to the changes of ATM content during long-term DI, we demonstrated using flow cytometry that the AT composition was changed at the end of the whole dietary intervention (i.e. after WM phase). This diet-induced AT remodelling was expressed by a...
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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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Effect of nutritional intervention on characteristics of adipose tissue in obese
Krauzová, Eva ; Štich, Vladimír (advisor) ; Müllerová, Dana (referee) ; Taxová Braunerová, Radka (referee)
Obesity is the world's most widespread metabolic disease and its continous rise in prevalence is alarming. The severity of obesity is that it is associated with a significant increase in the risk of metabolic diseases such as type 2 diabetes mellitus, hyperlipidemia, cardiovascular disease and some types of cancer. Obesity thus contributes significantly to increasing the cost of healthcare system. Preventing the aforementioned diseases is essential to reduce this burden. This is based both on the prevention of obesity itself, on the other hand, on the knowledge and consequent influence on the mechanisms of metabolic disorders associated with obesity. These disorders are based on changes in key metabolic organs: adipose tissue, liver, skeletal muscle and pancreas. The present thesis is focused on obesity- induced disorders of adipose tissue at the metabolic, endocrine and immune levels, presented as dysfunctional adipose tissue. Special attention was paid to the detrimental effect of elevated levels of basic macronutrients (carbohydrates and lipids) and, on the other hand, to the beneficial effects of low calorie diets on molecular characteristics of adipose tissue. The acquired knowledge illuminates the mechanisms of action of nutritional stimuli on adipose tissue dysfunction at the molecular and...
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Obesity and Obesogens
Dvořáková, Jana ; Müllerová, Dana (advisor) ; Houdek, Zbyněk (referee) ; Štich, Vladimír (referee)
The prevalence of obesity has already epidemic dimensions. Recently, the obesogens have been identified as the main cause in addition to excessive food intake, the lack of physical activity and the genetic background. These substances damage the metabolic processes, interfere with the hormonal functions and impair the energy balance in behalf of gaining weight and obesity. The theoretical part of this work deals with obesity, adipose tissue, lipid droplet and obesogens. From the obesogens there is closely specified a group of persistent organic pollutants (POP) from which one representative was used in the practical part of this work. The aim of the practical part was to describe the cellular model of differentiation the mesenchymal stem cell into adipocytes and to investigate the effect of one of the most frequently occurring obesogen on the expression genes of lipid metabolism and insulin signalling pathway. The morphological changes were observed in cells during differentiation (at days 0, 4, 10 and 21). The mesenchymal cells of the elongated spindle shape changed into adipocytes filled with lipid droplets. Oil Red O staining was used for quantification of accumulated lipids. The differentiation to adipocytes was confirmed by fluorescence immunocytochemistry using a specific protein FABP4. The...
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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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