非酒精性脂肪肝是因为肝细胞内脂肪过度堆积损害肝脏功能，并可诱发脂肪性肝炎、肝硬化或肝癌的病变。其发病过程复杂，目前对其认知依然十分有限。长链非编码RNA（lncRNA）的基因调控模式多样且调控范围广泛，是探索脂肪肝发病机制的理想突破口。我们新近发现，在肝脏和肝细胞中SRA（一种lncRNA）同促发脂肪肝的转录因子PPARγ有着紧密调控关系。这种调控对肝脏脂代谢基因表达的影响，可能是SRA缺失小鼠抵御高脂饮食诱导肝脂沉积的原因。为进一步阐明该调控模式的分子机制和病理意义，本项目拟进行以下工作：①寻找SRA介导下作用于PPARγ的辅因子；②分析SRA组蛋白修饰作用对PPARγ活性的影响；③在整体动物水平考察SRA调控PPARγ对脂肪肝发展的影响。本项目以PPARγ为引揭示SRA调节肝脏脂代谢的分子机制，为全面了解非酒精性脂肪肝的病理过程继而进行精准治疗打下基础。

Non-alcoholic fatty liver disease (NAFLD), formed by over-accumulation of fat in hepatocytes, damages the hepatic function and can lead to hepatosteatosis, cirrhosis or hepatocellular carcinoma. The complexity of NAFLD leads to the poor understanding of its pathogenesis. Due to the multiformity and universality in gene regulation, long non-coding RNA (lncRNA), become the ideal pathway to explore the mechanism of NAFLD. For the first time, we found that SRA, a kind of lncRNA, was deeply involved in the regulation of PPARγ, the transcriptional factor facilitating NAFLD development. This kind of regulation affects the expression of genes related to lipid metabolism, which results in the resistance of SRA deficient mice to high fat diet-induced hepatic steatosis. Measures would be taken to reveal the way and pathological significance that SRA regulates PPARγ: ①To search the cofactors interacting PPARγ in the mediation of SRA; ②To analyze the effect of SRA-induced histone modification on the activity of PPARγ; ③To analyze how the regulation of PPARγ by SRA affects the development of NAFLD in animals. Based on the study of PPARγ, this project reveals how SRA affects hepatic lipid metabolism, and lays the foundation for precise therapy of NAFLD.