细胞自噬通过调节脂质代谢、胰岛素抵抗、氧化应激、肝细胞损伤参与非酒精性脂肪肝（NAFLD）的发生。Tmem166/Eva1a是具有自噬调控作用的新分子，前期研究发现其在肝组织中高表达，通过PIK3CA-AKT-mTOR通路正向调控的细胞自噬参与了急性肝衰竭的发生发展。我们提出假设：高脂饮食状态下，Eva1a可以通过下调PIK3CA-AKT-mTOR通路增强肝细胞的噬脂作用，减少肝细胞内脂滴的积聚。本研究将在肝细胞特异敲除Eva1a基因的C57BL/6小鼠构建NAFLD模型，检测其表型、自噬水平、炎症因子、线粒体功能以及自噬调控通路的变化，分析Eva1a调控的自噬在NAFLD发生中的作用，并在应用CRISPR/Cas9基因编辑技术敲除该基因的PLC/PRF-5和L02细胞系中验证其作用机制。本研究为NAFLD的预防和治疗提供新的思路，具有重要的理论意义和应用价值。

Autophagy involves in the regulation of lipid metabolism, insulin resistance, oxidative stress and hepatocyte injury, and is closely related to the occurrence and development of NAFLD. Tmem166/Eva1a was identified as a novel human gene involved in autophagy regulation. Previous studies showed that Eva1a was highly expressed in liver tissues, and involved in the molecular regulation of autophagy in the occurrence and development of acute liver failure. Tmem166/Eva1a regulated autophagy level by acting on mTOR through the upstream pathway PIK3CA/AKT. We hypothesized that: Tmem166/Eva1a could enhance lipophagy through down-regulating the PIK3CA/AKT-mTOR pathway and reduce the accumulation of lipid droplets in hepatocyte on high-fat diet. This study aims to observe the effect of Cre-LoxP conditional Tmem166/Eva1a gene knockout on phenotype, autophagy level, inflammatory factors, autophagy level, damaged mitochondrial accumulation and proteins associated with regulation pathway in the NAFLD mouse models, and analyze the role of Tmem166/Eva1a-regulated autophagy in the occurrence of NAFLD, and constructing gene knockout PLC/PRF-5 and L02 cell line using CRISPR/Cas9 gene editing technology to further validate the molecular mechanism. This research is expected to provide a new idea in the prevention and treatment of NAFLD.