甘油三酯（Triglyceride，TG）在肝脏的沉积是非酒精性脂肪性肝病（non-alcoholic fatty liver disease，NAFLD）发生发展的核心环节。但TG在肝脏沉积的内在机制尚不明确。线粒体功能障碍在NAFLD发生发展中发挥重要的作用。既往研究多关注线粒体应激在NAFLD发生的“二次打击”中的作用。申请人前期研究发现高脂饮食下肝脏线粒体应激先于TG沉积的发生，且体内应用CyclophilinD抑制剂可改善高脂饮食引起的肝脏TG沉积，因此我们提出CyclophilinD介导的线粒体应激可能参与了高脂饮食诱导的肝脏TG沉积。申请人将在前期研究的基础上，在分子、细胞和整体三个水平，采用体内、体外相结合的的的方法，探讨线粒体应激在NAFLD发生发展中的作用及分子机制，并进一步探讨线粒体应激保护剂对NAFLD的预防作用，为临床预防和治疗NAFLD提供新的策略。

The hepatic triglyceride (TG) accumulation is the innitial step of the development of non-alcoholic fatty liver disease (NAFLD). However, the mechanism of hepatic TG accumulation is still not clear. Mitochondrial dysfunction plays an important role in the development of NAFLD. Previous studies have paid more attention to the role of mitochondrial stress in "second hit" of NAFLD. Our previous study found that hepatic mitochondrial dysfunciton is earlier that TG accumulation in the high-fat diet fed mice, and cyclophilin D inhibitor improves hepatic TG accumilation induced by high-fat diet feeding. Based on these results, we propose that cyclophilin D-mediated mitochondrial dysfunction may be involved in hepatic TG accumulation in NAFLD. In this project, we will explore the molecular mechanism of mitochondrial dysfunciton in the development of NAFLD by using in vitro and in vivo methods at molecular, cellular and holistic levels. Furthermore, we will explore the protective effect of mitochondria stress inhbitor on NAFLD, which will provide a new strategy for clinical prevention and treatment of NAFLD.