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

α-合成营养素(SNTA)是一种受体蛋白，其在肝脏中的功能尚不清楚。我们的小组已经证明，SNTA缺乏的小鼠在喂食高脂肪食物时，可以免受胰岛素抵抗、肝脏脂肪变性和肝脏炎症的保护。脂肪肝是发展为进行性肝病的危险因素。SNTA是在小鼠NASH中诱导的。SNTA缺乏是否能改善非酒精性脂肪性肝炎动物模型中的脂肪变性、炎症和纤维化，将在目前的应用中进行分析。本研究包括脂类成分的质谱分析。将对NASH模型中的肝脏免疫细胞的组成和炎症反应进行表征。SNTA在肝细胞脂质储存和肝星状细胞活化中的作用将被研究。脂多糖和胞壁二肽在巨噬细胞中的作用将在体外进一步分析。将分析新发现的SNTA调节/相关蛋白和描述良好的SNTA结合蛋白在SNTA-/-小鼠肝脏和小鼠非酒精性脂肪性肝病(NAFLD)中的表达。NAFLD是慢性肝病最常见的原因，我们小组的数据表明SNTA在胰岛素抵抗和NAFLD中起着作用。目前的项目打算进一步证实这些发现。

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.