Uloga glukokortikoidnih hormona u regulaciji energetskog metabolizma i inflamacije u jetri pacova nakon ishrane obogaćene fruktozom
The role of glucocorticoid hormones in regulation of energy metabolism and inflammation in the liver of fructose-fed rat
Doctoral thesis (Published version)
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One of the major causes of metabolic syndrome development is modern diet rich in fructose. Fructose-enriched diet initiates de novo lipogenesis, gluconeogenesis and chronic inflammation in the liver, which cumulatively lead to progress of insulin resistance. Glucocorticoid hormones are important regulators of energy metabolism that act antagonistically to insulin and may contribute to metabolic syndrome pathophysiology. Metabolic effects of glucocorticoids in the liver are usually attributed to their increased local regeneration, pointing to the importance of enzymes involved in prereceptor glucocorticoid metabolism. However, glucocorticoid receptor activation and modulation of its target genes expression are required for the regulation of gluconeogenesis, triglyceride synthesis and metabolic inflammation. The aim of this doctoral dissertation was to investigate the role of glucocorticoid signaling pathway in development of the metabolic syndrome symptoms, deregulation of energy metabolism and development of metabolic syndrome-associated inflammation in the liver of fructose-fed rat. In this study, two diet regimes were applied as a prerequisite for testing the type and degree of metabolic changes induced by different concentrations of fructose solution (10% and 60%). Morphological characteristics and biochemical alterations in the liver of male Wistar rats upon the nine-week fructose-rich diets were analyzed by combining standard experimental methods of biochemistry and molecular biology. Glucocorticoid signaling in the liver was examined at the level of prereceptor metabolism and the level of expression and activation of glucocorticoid receptor. Special attention was paid at investigation of lipid metabolism, metabolic inflammation and changes in insulin sensitivity.The results of this study showed that the long-term diets enriched in fructose (10% and 60%) led to increased circulating triglyceride concentration, but not to hyperglycemia, hyperinsulinemia or increase in body weight. However, only consumption of 60% fructose solution led to visceral obesity and an increase of relative liver mass. Fructose-enriched diet, regardless of concentration, affected prereceptor glucocorticoid metabolism in the rat liver,without changes in the concentration of corticosterone within the tissue, which is consistent with the absence of alterations in the glucocorticoid receptor activation and transcription of its target genes...
Keywords:Glucocorticoid hormones; De novo lipogenesis; Inflammation; Insulin resistance; Fructose; Liver
Source:University of Belgrade, Faculty of Biology, 2014, 1-141
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