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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 some genetic factors in bodyweight changes
Aldhoon, Bashar ; Hainer, Vojtěch (advisor) ; Kohoutová, Milada (referee) ; Vašků, Anna (referee)
The aim of the study was to determine the role of certain genetic factors on the ability to maintain weight loss, as well as to reduce the health risks associated with obesity in a group of about 300 obese patients followed for 2.5 years. The first part dealt with monitoring the impact of P73T polymorphism of the neuromedin gene on body weight reduction and its relation to certain metabolic and psychobehavioral factors. In the group of obese men, T allele non-carriers achieved significant reduction in waist circumference at the end of the follow-up. This waist circumference reduction was accompanied by a significant reduction in energy intake and by a significant decrease in the Beck depression score, while dietary restraint score increased. In the group of obese women, no significant differences between carriers and non-carriers of the T allele were observed. The significant reduction in total energy intake and macronutrient consumption was achieved in obese women regardless the genotype. In the second part, the effect of the Leu162Val of PPAR and Pro12Ala of PPAR gene polymorphisms on body weight reduction and on metabolic and psychobehavioral factors was studied in a group of 246 obese women. At baseline, non-carriers compared to carriers of the minor Val-allele of PPAR gene exhibitied a favorable effect...
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Growth hormone - IGF - 1 axis, it's regulation and function. Plasma ghrelin levels in certain pathologic states
Jarkovská, Zuzana ; Marek, Josef (advisor) ; Hainer, Vojtěch (referee) ; Mareš, Jan (referee)
Ghreliu is a peptide hormone with a strong stimulatory effect on growth hormone (GH) secretion. Ghrelin was origiu;i!íy isolated from the rat stomach as an endogenous secretagogue for the growth hormone secretagogue receptor (GHS-R). Although the fírst coinpoimds of the group of growth hormone seeretagogues were synthesized already in 1997, the isolation of the GHS-R and ghrelin is a matter of tlie last decade. Our study was aimed at the determination of the physiological role of endogenous ghrelin in GH secretion in certain pathological conditions and its associations with tlie GH/IGF-1 axis compounds. Our study was the first one detecíing also active ghrelin coucentrations. We assumed, that ghrelin secretion is aflected by the GH secretory statě. In patíents with acroinegaly we expected low ghrelin coucentrations (hypothesis 1) aud in patients with GHD we presuined, that ghrelin concentrations will be elevated (hypothesis 2) in comparison with healthy subjects as an effect of the negative feedback regulation by GH. Our findings however did not support tliese hypotheses, active and total ghrelin concentrations did not differ between patients and healthy controls. These data do not support an important role tor ghrelin in GH secretion in these conditions as well as the existence of a negative feedback...
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