近年来非酒精性脂肪肝（NAFLD）发病率呈现爆发式增长。然而，NAFLD病理过程复杂，发病机制尚未清楚阐明。SUMO是一种小分子肽，可以对靶蛋白进行修饰，并影响靶蛋白的定位，活性以及稳定性。SUMO化修饰是一种动态可逆过程，SENP2是重要的去SUMO化蛋白酶。研究表明，SENP2能够调节脂肪及肌肉组织代谢稳态，然而肝脏作为重要代谢器官，SENP2在肝脏代谢调控方面的作用尚不清楚。我们前期研究发现：SENP2在NAFLD发生过程中表达上调；肝脏特异性敲除SENP2后能够缓解肥胖小鼠肝脏的脂质堆积。本项目将基于前期发现，利用基因敲除鼠及细胞模型，以SENP2调节NAFLD发生发展为研究主线，深入探索SENP2对肝脏脂质代谢的调控作用，并挖掘SENP2调控NAFLD发生发展的分子机制。本项目的实施可为深入理解NAFLD病理过程提供理论基础，为临床治疗NAFLD提供新的靶点。

Recently, the morbidity of non-alcoholic fatty liver disease (NAFLD) has been explosively increased; However, the mechanism of which remains unclear due to the complex pathogenesis. Small ubiquitin-related modifier (SUMO) is a peptide, which can modify the target protein, thereby affecting the localization, activity or stability of the targets. SUMOylation is a dynamic and reversible process, with SENP2 as an important de-SUMOylation enzyme. It has been reported that SENP2 maintained metabolic homeostasis of adipose and muscle tissues; however, though liver is an essential place for metabolic control, role of SENP2 in regulating liver metabolism process is unknown. We previously found that SENP2 was upregulated during the development of NAFLD; and SENP2-deficient in liver could protect NAFLD induced by obesity. Based on our preliminary data, we aim to investigate the effect of SENP2 on NAFLD occurrence and lipid metabolism in liver, and clarify the underlying mechanism, by studying in the gene knockout mice and cell model. This study might deepen the understanding of NAFLD pathogenesis, and help to identify novel therapeutic target for NAFLD intervention.