肝脏脂质代谢失衡是诱发非酒精性脂肪性肝病（NAFLD）的关键，其发生机制复杂，是国际前沿研究中重要的科学问题。目前临床缺乏有效药物纠正肝脏脂质代谢紊乱，因此，寻找维持肝脏脂质代谢稳态的关键分子和干预脂质代谢紊乱的有效靶点，具有重要科学意义。项目组前期发现一个研究甚少的蛋白WDR6,其表达与肝脏甘油三酯（TG）含量正相关。WDR6转基因小鼠肝脏TG增多,而WDR6敲除小鼠肝脏TG降低，提示WDR6对维持肝脏脂质代谢稳态至关重要，但其机制不清。本项目拟采用体内（肝脏特异性敲除/敲入小鼠模型）和体外（肝原代细胞和细胞株）结合策略,采用多学科技术,研究①明确WDR6调节肝脏脂质代谢的生理功能，②论证WDR6调控肝脏脂质代谢的分子机制，③循证医学验证及动物水平探索干预WDR6预防及改善NAFLD的应用价值，论证“WDR6蛋白调控肝脏脂质代谢稳态作用和机制”科学假说，为治疗肝脏脂代谢紊乱提供潜在靶点。

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver.disease and is strongly associated with liver lipid metabolism disorder.Up to date, there is no effective treatment for NAFLD, for the reason that the therapeutic target which is responsible for regulation of lipid metabolism remainsunclear. In our previous research, WDR6, which is a less reported protein, wasfound in a positive correlation with liver triglyceride (TG) level. WDR6 transgenic mouse model (WDR6-Tg) showed increased liver TG contents, on the contrary, mice with WDR6 deficiency (WDR6-KO) were obviously lower in liver TG. These results had demonstrated that WDR6 might be associated in lipid metabolism, but the mechanisms is not clear indetail. Our project, based on genetic manipulating mouse model, primary hepatocytes and cell lines, intends to demonstrate the possible role of WDR6 in liver lipid disorders, in the following aspects: ①the physiological functions of WDR6 in regulating liver lipid metabolism,②the detailed mechanism of WDR6 in the regulation of liver lipid metabolism. ③the possible exploration of WDR6 in the prevention and improvement of NAFLD in the clinic and mouse models.