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Circadian rhythms in adipocytes and impact of their disruption
Zavřelová, Michaela ; Sumová, Alena (advisor) ; Spišská, Veronika (referee)
This bachelor thesis deals with circadian rhythms in adipocytes and the consequences of their disruption. The thesis summarizes current scientific knowledge and explores the mechanism of rhythm control at the molecular level, which is formed by transcriptional translational feedback loops. Adipocytes control lipid metabolism through the production of adipokines, adipogenesis, lipogenesis, and lipolysis. The research focuses on how clock genes are involved in these processes. All of these events, which are characteristic of adipocytes, are highly regulated and the genes that are involved in them are transcriptionally activated by clock gene proteins. Circadian rhythms are an integral part of our lives, and desynchronization of rhythms between the main oscillator, which is the suprachiasmatic nuclei, and peripheral adipocytes can lead to metabolic disorders, which in turn can lead to obesity, insulin resistance, or type 2 diabetes. Obesity is one of the biggest problems of modern society, and disrupted circadian rhythms due to today's lifestyle are one of the causes of its development. Key words: circadian rhythms, clock genes, adipocytes, obesity, PPARγ, adipogenesis, lipogenesis, lipolysis, leptin, adiponectin
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Pharmacological modifications of potential signal systems regulating metabolism of adipocytes and hepatocytes and their influence on obesity
Hodis, Jiří ; Farghali, Hassan (advisor) ; Kršiak, Miloslav (referee) ; Otová, Berta (referee)
v anglickém jazyce: Thesis abstract: Background and aims: Both obesity and metabolic syndrome form severe health problems in the whole world. Nevertheless the armament of pharmacotherapy for both diseases remains unsatisfactory. We aimed our work to main organs in risk of the mentioned diseases -liver and visceral fat using hepatocytes and visceral adipocytes as model. We detected 3 main metabolic and signalization activities- glycogenolysis, Nitric oxide (NO) production and transcription of inducible NO synthase (iNOS) in hepatocytes, lipolysis, NO production and iNOS transcription rate in adipocytes. We directed our interest to combination of peroxisome proliferation activator receptor γ (PPARγ) agonist, antagonist and β3 adrenergic agonist in the culture of epididymal rat adipocytes in the first part of our work. While in the second part we investigated the influence of β and α adrenergic mimetics, adrenergic blockers in the culture of rat high glycogen content hepatocytes. Methods: NO production was detected under the active agents treatments by detection of NO oxidative products NO2 and NO3 in media. Glycogenolysis was measured as free glucose rise released by hepatocytes into the media. NOS transcription level was extrapolated after comparative polymerase chain reaction with reverse...
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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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Endocrine role of adipose tissue in the pathogenesis of chronic inflammation in obesity and type 2 diabetes mellitus
Kratochvílová, Helena ; Haluzík, Martin (advisor) ; Taxová Braunerová, Radka (referee)
Adipose tissue as an active endocrine organ is explored in a number of processes associated with metabolic disorders. This work is aimed on studying the effect of endoscopically implantable weight-reducing device - duodeno-jejunal bypass liner - on subclinical inflammation of adipose tissue in obese patients, which contributes to the development of type 2 diabetes mellitus. Specifically, for patients implanted with duodeno- jejunal bypass liner we determined anthropometric, biochemical and hormonal characteristics, and mRNA expression of subcutaneous adipose tissue proinflammatory (TNF-α, leptin, CCL- 2, CX3CL1, CD40, CD80, CD86, CD206, CD163 and IL-6) and anti-inflammatory genes (Adiponektin, IL-10) before, one month and ten months after the intervention. The implantation of duodeno-jejunal bypass liner significantly decreased body weight, waist circumference, and improved metabolic and glycemic control. In addition, C-reactive protein a highly sensitive indicator of inflammatory processes in the body was reduced ten months after implantation. In the case of mRNA expression of CD86 (a marker of activated B lymphocytes and macrophages) there was temporarily increase in adipose tissue one month after the surgery and the subsequent significant decrease after ten months. mRNA expression of other...
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Role of Gq-coupled receptors in brown adipocytes
Čajková, Michaela ; Kovařík, Miroslav (advisor) ; Doleželová, Eva (referee)
Charles university in Prague, Pharmaceutical faculty in Hradci Králové, Department of biological and medical sciences Rheinische Friedrich-Wilhelms-University Bonn, Institute of Pharmacology and Toxicology Candidate: Michaela Čajková Supervisor: PharmDr. Miroslav Kovařík, Ph.D. Consultant: Dr. Linda Sarah Hoffmann Title of diploma thesis: Role of Gq-coupled receptors in brown adipocytes In my diploma thesis, we focused on four Gq-coupled receptors (F2R, LPHN1, α1DAR, TSHR) in brown adipocytes (BAs), which were identified in the screen as the highest expressed in immature and mature BAs. Our goal was to validate suggestion, that Thyroid stimulating hormone receptor (TSHR) plays a key role in differentiation of BAs and that F2R, LPHN1, α1D-AR might be important for BAs. In our study, we investigated gene expression of these four receptors in BAs, using analytical methodsquantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot. Results from analysis revealed, that expression of TSHR was increased in mature BAs, it means, that TSHR induce differentiation of BAs. The BAs transduced with short hairpin RNA (sh-RNA) against TSHR were less differentiated, this we proved also with Oil Red-O staining. Expression of adipocyte Protein 2 (aP2), peroxisome proliferator-activated...
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The role of adipose tissue in the pathophysiology of obesity and anorexia nervosa
Kratochvílová, Helena ; Haluzík, Martin (advisor) ; Pavlišová, Jana (referee)
The view of adipose tissue and its significance in human pathophysiology has changed substantially in the recent couple of years. It has been shown that adipose tissue is not only a passive storage site for excess energy, but that it actively participates in the maintenance of whole-body homeostasis as an endocrine organ producing various hormones and other biologically active molecules, which by acting in an endocrine, paracrine as well as autocrine fashion affect different organs and systems. An intact regulation of adipose tissue processes plays an important role in sustaining the integrity of the organism, whereas its defects lead to the development of a number of diseases. This thesis focuses primarily on the significance of adipose tissue in the pathogenesis of obesity and anorexia nervosa. In the last years, the incidence of obesity rapidly increases ranking, along with its complications, among the world's leading health problems. Obesity is associated with endocrine dysfunction of adipose tissue characterized by disrupted production of adipose tissue hormones and cytokines resulting in the development of numerous disorders including type 2 diabetes mellitus and cardiovascular diseases. A completely opposite disorder, where, however, adipose tissue, or more precisely the absence of it, plays...
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Pharmacological modifications of potential signal systems regulating metabolism of adipocytes and hepatocytes and their influence on obesity
Hodis, Jiří ; Farghali, Hassan (advisor) ; Kršiak, Miloslav (referee) ; Otová, Berta (referee)
v anglickém jazyce: Thesis abstract: Background and aims: Both obesity and metabolic syndrome form severe health problems in the whole world. Nevertheless the armament of pharmacotherapy for both diseases remains unsatisfactory. We aimed our work to main organs in risk of the mentioned diseases -liver and visceral fat using hepatocytes and visceral adipocytes as model. We detected 3 main metabolic and signalization activities- glycogenolysis, Nitric oxide (NO) production and transcription of inducible NO synthase (iNOS) in hepatocytes, lipolysis, NO production and iNOS transcription rate in adipocytes. We directed our interest to combination of peroxisome proliferation activator receptor γ (PPARγ) agonist, antagonist and β3 adrenergic agonist in the culture of epididymal rat adipocytes in the first part of our work. While in the second part we investigated the influence of β and α adrenergic mimetics, adrenergic blockers in the culture of rat high glycogen content hepatocytes. Methods: NO production was detected under the active agents treatments by detection of NO oxidative products NO2 and NO3 in media. Glycogenolysis was measured as free glucose rise released by hepatocytes into the media. NOS transcription level was extrapolated after comparative polymerase chain reaction with reverse...
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