VMP1 regulates hepatic lipoprotein secretion and NASH independent of autophagy

VMP1 is an ER membrane protein with phospholipid scramblase activity that has a critical role in regulating phagophore expansion and autophagosome closure. VMP1 also regulates lipid droplet formation and lipoprotein secretion in cultured cells and zebrafish. In a recent study, we showed that mice with hepatic deletion of Vmp1 have impaired very-low-density lipoprotein (VLDL) secretion and develop nonalcoholic steatohepatitis (NASH) even when fed with regular chow diet. Mechanistically, deletion of Vmp1 leads to decreased hepatic phosphatidylcholine (PC) and phosphatidylethanolamine (PE) levels as well as altered PC and PE acyl chain compositions resulting in the accumulation of neutral lipid structures in the ER phospholipid bilayer and decreased pre-VLDL assembly. These studies provide novel mechanistic insights into the non-autophagic functions of VMP1 in regulating lipoprotein secretion.