• Experimental medicine.
  • Updated 28.04.2017 by Administrator UMB

    Experimental medicine

    The consumption of food rich in sugars and saturated fatty acids (SFA) is on the rise in Western societies. This is implicated as the main cause of non-alcoholic fatty liver disease (NAFLD), whose progression to nonalcoholic steatohepatitis (NASH) is a leading risk factor for development of insulin resistance and Type 2 diabetes. Subsequently, more severe hepatic disease such as cirrhosis and hepatocellular carcinoma may also occur. The precise mechanisms by which excessive fat and sugar intake promote NAFLD/NASH may include increased provision of energy substrates (glucose and SFA) mainly regulated by membrane transporters and/or impaired mitochondrial capacity for oxidation, which leads to liptotoxic effects. Previous studies with animal models indicate that both high fat and high sugar feeding can independently induce many characteristics of NAFLD/NASH. However, the precise contributions of protein mediated transport of energy substrates (FAT/CD36, FATP`s, FABPpm, GLUT2, etc.) to the hepatocytes remain poorly resolved. Thus, a central hypothesis to be tested in this proposal is that excessive dietary fat and sugar promote NAFLD/NASH through may be different but complementary mechanisms. We aim to characterize the specific and synergistic effects of excessive fat and sugar feeding on two central loci of NAFLD/NASH pathogenesis:1) rearrangement of hepatic energy substrates fluxes regulated by membrane proteins and 2) metabolic consequences of excessive energy provision on liver metabolism (e.g. impaired FA oxidation, excessive lipid accumulation, induction of insulin resistance, generation of bioactive lipid species such as ceramide and others).