Evaluation of TrkB role on non-alcoholic fatty liver disease (NAFLD) in mice

Abstract

Non-alcoholic Fatty Liver Disease (NAFLD)affects baout 20% of world population and is being considered the hepatic manifestation of metabolic syndrome. It is chacterized by fat accumulation (steatose) and may evolve to non-alcoholic steato-hepatitis (NAS), the more severe form of the disease, which can progress to cirrosis or hepatocarcinoma.Brain derived neurotropic factor (BDNF)has its signaling pathway trough its receptor, Tyrosine Kinase Receptor, isoform b (TrkB), mediating neuron survival, differentiation and plasticity, and its role in brain is essential for appetite control.In liver, BDNF/TrkB pathway has a repressor effect on oxidation/exportation of fatty acids, promoting steatosis. Hepatic-specific deletion of this pathway has a protective effect against deleterious effects of high fat diet over triglycerides and glucose metabolism in liver.In our previous studies, we found TrkB expression to be about 20x higher in liver of FVB/N animals comparing to C57Bl6/J and when challenged with high fat diet FVB/N mice develop pronounced steatosis when compared to C57Bl6/J.Considering the pronounced effect of TrkB in energy balance and crescent interest using TrkB agonists as anti-obesity drugs, troughout its anorexigenic feature in central nervous system, it is indispensable to evaluate its role in development of NAFLD in liver. (AU)