National Repository of Grey Literature 2 records found  Search took 0.01 seconds. 
Mechanisms underlying the development of insulin resistance in liver steatosis
Papáčková, Zuzana ; Cahová, Monika (advisor) ; Macek Jílková, Zuzana (referee)
We tested the hypothesis that triacylglycerol (TAG) accumulation in the liver induced by short-term high-fat diet (HFD) in rats leads to the dysregulation of endogenous TAG degradation via lysosomal pathway and is causally linked with the development of hepatic insulin resistance. Lysosomal lipase (LAL) is stored in qualitatively different depots (light and dense lysosomes). In contrast to dense lysosomal fraction, LAL associated with light lysosomes exhibits high activity on intracellular TAG and prandial- or diet-dependent regulation. On standard diet, LAL activity was up-regulated in starved and down-regulated in fed animals. In the HFD group, we demonstrated elevated LAL activity, increased TAG content, enhanced production of diacylglycerol and the abolishment of prandial-dependent LAL regulation in light lysosomal fraction. The impairment of insulin signalling and increased activation of PKCε was found in liver of HFD-fed animals. Lipolysis of intracellular TAG, mediated by LAL, is increased in steatosis probably due to the enhanced formation of phagolysosomes. Consequent overproduction of diacylglycerol may represent the causal link between HFD-induced hepatic TAG accumulation and hepatic insulin resistance via PKCε activation.
Integrating Role of Adipose Tissue Secretory Functions in Response to Dietary and Pharmacological Treatments
Macek Jílková, Zuzana ; Kopecký, Jan (advisor) ; Müllerová, Dana (referee) ; Cahová, Monika (referee)
Obesity represents a predominant risk factor for the development of metabolic diseases like type 2 diabetes mellitus and it is characterized by adipocyte hypertrophy. The size of adipocytes influences the adipocytes biology and secretory functions of adipose tissue in general. Understanding the mechanisms regulating growth and secretory activity of adipose tissue is of paramount importance. Moreover, obesity represents a chronic subclinical inflammatory state linking obesity to insulin resistance and hypertrophic adipocytes contribute to this phenomenon. An improvement of strategies used in the prevention and treatment of inflammation associated with obesity is therefore urgently needed. The four studies described in this thesis address several topics related to adipose tissue biology, and thus contributing to the understanding of the integrating role of adipose tissue secretory functions in response to dietary and pharmacological treatments. This thesis demonstrates a possible role of white adipose tissue thyroid hormones (TH) metabolism in the modulation of its function under conditions of changing adiposity (Publication A); a unique role of leptin, secreted from adipose tissue, in the complex control of energy homeostasis of the organism (Publication B); beneficial effects of the combination treatment of...

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