非酒精性脂肪性肝病（NAFLD）是与肥胖、2型糖尿病相关的代谢性疾病，可发展至肝衰竭及肝癌，成为亟待解决的健康问题。运动是首选治疗，阐明运动防治NAFLD分子机制以期靶向模拟干预有助于改善无法耐受运动病人的预后。微小RNA参与NAFLD，但是否参与介导运动对NAFLD的保护尚待阐明。我们前期研究显示：运动改善小鼠NAFLD伴随miR-212下调；细胞水平过表达miR-212可导致肝细胞脂质沉积，抑制miR-212具有反向作用，机制研究发现该过程由其靶基因FGF-21介导。此外预测发现锌指转录因子EGR1是肝脏中miR-212上游调控因子。本项目拟通过体内外实验研究miR-212模拟运动保护NAFLD的机制，验证“EGR1/miR-212/FGF-21通路是运动防治NAFLD调控通路”假说。调控该通路或可模拟运动改善NAFLD，成为治疗靶点，为后期研发NAFLD治疗新工具提供前期实验基础。

Non-alcoholic fatty liver disease (NAFLD) , a common metabolic-related disease associated with obesity and diabetes ,has become an urgent health problem. Exercise is in the frontline for NAFLD patient management. Clarifying the molecular mechanism of exercise in protecting NAFLD in order to target the key pathway and mimic its role may help to improve the prognosis of patients who cannot tolerate exercise. MicroRNAs (miRNAs, miRs) have been reported to contribute to NAFLD, however, its role in exercise-induced protection against NAFLD is needed to be clarified. Our previous studies have found that exercise could attenuate mouse NAFLD, accompanied by the down-regulation of miR-212 . Meanwhile, overexpression of miR-212 in vitro could lead to the deposition of lipid in hepatocytes, whereas the inhibition of miR-212 had the opposite effect, which was mediated by its target gene FGF-21. In addition, it was predicted that EGR1, a zinc finger transcription factor, was a potential upstream regulator of miR-212 in liver. This project is intended to further investigate the role of miR-212 in exercise-induced protection against NAFLD and its molecular mechanism in vitro and in vivo, and thus to verity our hypothesis that EGR1 / miR-212 / FGF-21 may be a key pathway in exercise protection for NAFLD. Regulating EGR1 / miR-212 / FGF-21 pathway may improve NAFLD by mimicking the effect of exercise and become the target of NAFLD treatment. This project may provide an experimental basis for the later development of new tools for the treatment of NAFLD.