Implications of Sortilin in Lipid Metabolism and Lipid Disorder Diseases

The present review provides a summary of recent evidence of sortilin expression, function, and regulation and its implications in lipid metabolism and development of lipid disorder diseases. As a member of the vacuolar protein sorting 10 protein (Vps10p) receptor family, sortilin mediates intracellular trafficking of diverse endogenous or exogenous protein substrates between the trans-Golgi network (TGN) and plasma membrane compartments. Recent studies reveal that sortilin regulates the expression of lipid genes, plasma lipid level, and the development of lipid disorder diseases. Sortilin promotes atherogenesis by regulating hepatic very low density lipoprotein (VLDL) secretion and plasma lipid level and subsequently macrophage lipid accumulation. Sortilin deficiency is caused by accelerated proteasome degradation under insulin resistance conditions and is thereby implicated in the hyperlipidemia of type 2 diabetes mellitus (T2DM). Sortilin facilitates hepatic cholesterol accumulation by inhibiting hepatic cholesterol catabolism, which promotes the development of nonalcoholic fatty liver disease (NAFLD). Sortilin plays an important role in lipid metabolism and represents a promising therapeutic target for lipid disorder diseases.