肝脏脂肪蓄积是脂肪性肝病的始动因素，与多种慢性代谢性疾病显著相关。脂肪营养蛋白（PNPLA3）具有脂肪合成和水解的双重功能，其I148M突变所引起的肝脏脂肪蓄积的机制还未有定论。课题组前期的研究发现，PNPLA3 rs738409与血浆甘油三酯（TG）水平存在一定的交互作用。我们假设该交互作用参与了肝脏脂肪蓄积的调节。基于此，我们拟首先建立高甘油三酯血症大鼠模型，通过基因表达水平的改变分析血清TG水平、PNPLA3 I148M突变以及两者的交互作用对大鼠肝脏脂肪蓄积的影响。以大鼠原代肝细胞和HepG2细胞为研究对象，体外层面分析该交互作用对肝细胞脂肪蓄积的影响，同时检测脂肪合成及分解通路关键基因和蛋白的表达水平进行初步的机制研究。本项目的实施将为肝脏脂肪蓄积的机制研究提供一定的思路，也有利于从遗传和环境方面早期发现相关疾病的高危人群，具有重要的理论意义和应用价值。

Hepatic fat accumulation is not only the initiating factor of fatty liver disease, but also associated with a variety of chronic metabolic diseases. Adiponutrin (PNPLA3) possesses both lipolysis and lipogenesis functions, and its I148M variant is involved in the regulation of hepatic fat accumulation. However, the specific mechanism remains unclear. Our previous studies have found that there existed an interaction between PNPLA3 rs738409 (I148M) and plasma triglyceride concentrations. Based on the hypothesis that the above interaction takes part in the regulation of hepatic fat accumulation, the present study will be designed to build hypertriglyceridemia rat model to evaluate the effects of serum triglyceride concentrations, PNPLA3 I148M variant, and its interaction on hepatic fat accumulation by altered gene expression levels. Moreover, we further discuss the potential influence in primary rat hepatocytes and HepG2 cell lines under oleic acid treatment and the application of RNAi technology. Meanwhile, the expression levels of key genes and proteins participated in the lipogenesis and lipolysis pathways will be detected to explore the underlying mechanism. The implementation of the present project is not only useful to provide new clues for the mechanism of hepatic fat accumulation, but also helpful to the early detection of high risk populations, with theoretical significance and application value.