非酒精性脂肪肝病（NAFLD）被认为是代谢综合征在肝脏的表现。SIRT2作为NAD+依赖的去乙酰化酶，能调节多种能量和代谢过程。我们前期研究首次发现：1，NAFLD模型中SIRT2表达明显降低，高表达SIRT2后可改善肝细胞内脂肪沉积，此现象依赖于SIRT2去乙酰化作用，提示SIRT2与NAFLD密切相关，可能作为NAFLD的治疗靶点；2，SIRT2能够结合并调控HNF4α蛋白表达，而后者被证实是脂代谢的关键调控因子。因此我们推测SIRT2可能通过去乙酰化调控HNF4α及其相关信号而改善NAFLD。本课题拟以NAFLD芯片数据、动物模型及细胞模型为研究对象，结合细胞生物学和分子生物学方法，探究SIRT2改善NAFLD的作用，并将逐步揭示SIRT2-HNF4α在NAFLD形成中的调控网络，为SIRT2成为NAFLD治疗的可能靶点提供新的科学依据。

Nonalcoholic fatty liver disease (NAFLD) is regarded as a manifestation of metabolic syndrome in the liver. SIRT2 is a NAD+-dependent deacylase with an important role in energy metabolism modulation. However, the association of SIRT2 with NAFLD remains unclear. Our previous works showed that (1) SIRT2 expression was significantly decreased in different models of NAFLD. Furthermore, SIRT2 overexpression improved hepatic steatosis，whereas deacetylation inactivation of SIRT2 was not able to improved hepatic steatosis. These results suggested that SIRT2 might implicate in the development of NAFLD. (2) SIRT2 could bind to and regulate HNF4α, the key regulatory factor of lipid metabolism. Thus, we hypothesized that SIRT2 might bind to and reduce HNF4α acetylation level, and subsequently alleviate NAFLD. By using microarray data, different mouse models and cellular models of NAFLD, we will further clarify the specific mechanisms of SIRT2 in the improvement of NAFLD, and reveal the network of SIRT2/ HNF4α involved in the pathological progress of NAFLD, and provide evidences that SIRT2 could be used as a promising clinical therapeutic target for the prevention of NAFLD.