Role of alpha-syntrophin in non-alcoholic fatty liver disease

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Alpha-Syntrophin (SNTA) is an adaptor protein whose function in the liver has not been clarified yet. Our group has shown that SNTA deficient mice are protected from insulin resistance, liver steatosis and hepatic inflammation when fed a high fat diet. Fatty liver is a risk factor to develop progressive liver disease. SNTA is induced in murine NASH. Whether SNTA deficiency ameliorates steatosis, inflammation and fibrosis in animal models of non-alcoholic steatohepatitis will be analyzed in the current application. This study includes analysis of lipid species by mass spectrometry. The composition and inflammatory response of hepatic immune cells in the NASH models will be characterized. The role of SNTA in hepatocyte lipid storage and activation of hepatic stellate cells will be studied. The effect of lipopolysaccharide and muramyldipeptide in macrophages will be further analyzed in-vitro. The expression of newly identified SNTA regulated / associated proteins and of well-described SNTA binding proteins will be analyzed in SNTA-/- mice liver and in murine non-alcoholic fatty liver disease (NAFLD). NAFLD is the most prevalent cause of chronic liver disease and data from our group suggest a role of SNTA in insulin resistance and NAFLD. The current project intends to further corroborate these findings.