脂肪肝是由于肝细胞内脂肪堆积过多所导致的病变,已成为影响人类健康的常见病。极低密度脂蛋白（VLDL）的组装和分泌缺陷是影响肝脏和血液脂代谢平衡的一个主要原因，虽然已经鉴定出一些蛋白因子与VLDL的组装和分泌相关，但是其作为生物大分子复合物是如何在内质网上合成，并运输到血液中的具体过程目前还不清楚。近年的研究表明，MEA6和Tango1可能与囊泡复合体COPII成员互作，共同参与胶原大分子从内质网离开和分泌到细胞外基质的过程。为了研究MEA6的生理功能，我们制备了MEA6基因的条件性敲除小鼠模型并发现MEA6全身敲除小鼠胚胎致死。在肝脏中特异敲除MEA6后导致严重的脂肪肝以及血浆中各种脂类的显著降低，这提示MEA6可能也参与了VLDL的分泌。本研究将利用基因敲除的小鼠模型，同时结合细胞生物学、蛋白质组学、脂组学和生化手段对MEA6在脂肪代谢过程中的生理作用和分子机制进行系统研究。

Fatty liver is caused by the abnormal storage of lipids in the liver. Disturbance of VLDL secretion and lipid metabolism is one of the most prevalent chronic liver diseases worldwide. Secretion of very-low-density lipoprotein (VLDL) plays a very important role in the regulation of triglyceride (TG) and cholesterol levels in the liver and plasma. MEA6 interacts with components of the COP II complex and Tango I and together, they play an essential role in Collagen VII transportation. Through the generation of conditional knockout mice, we found that MEA6 is critical for secretion of lipid and lipoprotein from the liver. Liver-specific knockout of MEA6 leads to severe fatty liver accompanied by hypolipaemia and ER stress. In the present study, the physiological function and the molecular mechanism of MEA6 in lipid metabolism will be explored using gene knockout mouse model in combination with proteomics, lipidomics and biochemistry means.