This thesis focuses on the effects of n-3 polyunsaturated fatty acids (n-3 PUFA) on development of non-alcoholic fatty liver disease (NAFLD) in experiment, on prevalence of this condition in patients with type 2 diabetes mellitus and metabolic syndrome and also on non-invasive diagnostics. The aim was to study the effect of n-3 PUFA on NAFLD development in an experimental model and based on analysis of a group of patients with type 2 diabetes and metabolic syndrome to assess the prevalence of this condition. Lastly we aimed to evaluate non-invasive diagnostic methods of liver fibrosis and NASH. We demonstrated beneficial effects of n-3 PUFA administration on NAFLD development in a C57/Bl6 mice high fat methionin-cholin defficient dietary model of NAFLD. n-3 PUFA administration led to biochemical improvement, decrease of lipid accumulation in the liver as well as improvement of histology. These effects are determined by complex modulation of lipid metabolism, mainly due to decrease in availability of fatty acids for triglyceride synthesis in the liver, changes of adipokine levels and amelioration of proinflammatory status in the liver. In a group of type 2 diabetics we found NAFLD prevalence of almost 80%, 14% of these patients had also signs of liver fibrosis or cirrhosis. Non-invasive methods...

NOVEL METABOLIC REGULATORS AND PROINFLAMMATORY FACTORS IN THE ETIOPATHOGENESIS OF TYPE 2 DIABETES MELLITUS AND OBESITY: THE INFLUENCE OF PHARMACOLOGICAL AND DIETARY INTERVENTIONS MUDr. Miloš Mráz Doctoral Thesis ABSTRACT (EN) Identifying novel factors involved in the etiopathogenesis of obesity, diabetes mellitus and their complications has become one of the primary scopes of metabolic research in the last years. The aim of the present study was to evaluate the role of recently discovered metabolic and inflammatory regulators including fibroblast growth factors 19 and 21 and chemotactic cytokines in the development of obesity and type 2 diabetes mellitus (DM2). A total number of 182 patients were included into the study. They were divided into 3 groups - patients with obesity but without type 2 diabetes mellitus, individuals with obesity and type 2 diabetes mellitus and healthy control normal-weight subjects. Selected interventions included 2 to 3 weeks of very-low-calorie diet (VLCD - energy content 2500 kJ/day), 3 months of administration of PPARα receptor agonist fenofibrate and acute hyperinsulinemia during hyperinsulinemic isoglycemic clamp. Our results indicate that the increase of circulating FGF-21 levels after VLCD and fenofibrate treatment could contribute to positive metabolic effects of these...