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

α-突触营养蛋白（SNTA）是一种衔接蛋白，其在肝脏中的功能尚未阐明。我们的研究小组已经表明，SNTA缺陷小鼠在喂食高脂肪饮食时受到胰岛素抵抗、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在鼠NASH中被诱导。SNTA缺乏是否改善非酒精性脂肪性肝炎动物模型中的脂肪变性、炎症和纤维化将在本申请中进行分析。本研究包括通过质谱法分析脂质物质。将表征NASH模型中肝脏免疫细胞的组成和炎症反应。将研究SNTA在肝细胞脂质储存和肝星状细胞活化中的作用。脂多糖和胞壁酰二肽在巨噬细胞中的作用将在体外进一步分析。将在SNTA-/-小鼠肝脏和鼠非酒精性脂肪性肝病（NAFLD）中分析新鉴定的SNTA调节/相关蛋白和充分描述的SNTA结合蛋白的表达。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中的作用。本项目打算进一步证实这些调查结果。

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.