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Regulation of lipolysis and re-esterification in white adipose tissue - possible role of FGF21
Špiláková, Blanka ; Zouhar, Petr (advisor) ; Šilhavý, Jan (referee)
Fibroblast growth factor 21 (FGF21) is a unique peptide hormone involved in the energy homeosta- sis, as well as in the regulation of glucose and lipid metabolism. Numerous animal studies suggest that FGF21 may be used as a potential treatment for obesity and type 2 diabetes mellitus. It was found out, that FGF21 counteracts the development of obesity presumably by increasing energy expenditure through activation of thermogenesis in brown and white adipose tissue. FGF21 apparently also inhibits lipolysis. However, the specific mechanism of action of FGF21 is not clear. In our experiments we studied the antiobesogenic effects of FGF21 on mice model of diet-induced obesity at thermoneutrality. It is assumed that this model approach (in contrast to housing mice at standard laboratory temperature) mimics closely the metabolic status of humans. During the 4- to 8-day FGF21 treatment we observed a gradual reduction of lipid content in the brown and white adipose tissue and liver, especially in combination with β3-adrenergic stimulation. We have confirmed that FGF21 inhib- its lipolysis and also stimulates browning in certain adipose tissue depots. Furthermore, we have found that the effect of FGF21 on fatty acid secretion by adipose tissue is not mediated by changes in the fatty acid re-esterification...
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The role adipose tissue in development of insulin resistance and other metabolic disorders in patients with pheochromocytoma
Klímová, Judita ; Petrák, Ondřej (advisor) ; Kříž, Jan (referee) ; Mlíková Seidlerová, Jitka (referee)
Pheochromocytoma and functional paraganglioma (PPGL) are rare neuroendocrine tumors characterized by catecholamines overproduction, which give a rise to disorders of glucose, lipid, and energy metabolism. The role of adipose tissue in these processes remains unclear. Our aim was to determine the gene expression profile in subcutaneous and visceral adipose tissue of patients with PPGL focusing on endocrine functions of adipose tissue, occurrence of brown (BAT) and beige adipose tissue (BeAT), all in connection with other measured metabolic and energy parameters and levels of circulating adipokines. We demonstrate signs of UCP1-dependent norepinephrine induced thermogenesis connected with overexpression of DIO2 in retroperitoneal VAT of PPGL and higher expression of key transcriptional factors of brown/beige adipogenesis, namely PPARGC1α, CEBPB and PRDM16. However, classic murine BAT or BeAT gene signature in VAT of PPGL was not detected. In subcutaneous adipose tissue (SAT) of PPGL we found signs of possible BeAT transformation, however without simultaneously undergoing UCP1-dependent thermogenesis. We also demonstrate that patients with PPGL have higher serum levels of FGF21 compared to healthy controls and these levels do not differ from obese patients. Furthermore, successful tumor removal...
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Regulation of lipolysis and re-esterification in white adipose tissue - possible role of FGF21
Špiláková, Blanka ; Zouhar, Petr (advisor) ; Šilhavý, Jan (referee)
Fibroblast growth factor 21 (FGF21) is a unique peptide hormone involved in the energy homeosta- sis, as well as in the regulation of glucose and lipid metabolism. Numerous animal studies suggest that FGF21 may be used as a potential treatment for obesity and type 2 diabetes mellitus. It was found out, that FGF21 counteracts the development of obesity presumably by increasing energy expenditure through activation of thermogenesis in brown and white adipose tissue. FGF21 apparently also inhibits lipolysis. However, the specific mechanism of action of FGF21 is not clear. In our experiments we studied the antiobesogenic effects of FGF21 on mice model of diet-induced obesity at thermoneutrality. It is assumed that this model approach (in contrast to housing mice at standard laboratory temperature) mimics closely the metabolic status of humans. During the 4- to 8-day FGF21 treatment we observed a gradual reduction of lipid content in the brown and white adipose tissue and liver, especially in combination with β3-adrenergic stimulation. We have confirmed that FGF21 inhib- its lipolysis and also stimulates browning in certain adipose tissue depots. Furthermore, we have found that the effect of FGF21 on fatty acid secretion by adipose tissue is not mediated by changes in the fatty acid re-esterification...
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