Complex role of autophagy in regulation of hepatic lipid and lipoprotein metabolism.

Discovering new therapeutic interventions to treat lipid and lipoprotein disorders is of great interest and the discovery of autophagy as a regulator of lipid metabolism has opened up new avenues for targeting modulators of this pathway. Autophagy is a degradative process that targets cellular components to the lysosome and recent studies have indicated a role for autophagy in regulating hepatic lipid metabolism (known as lipophagy) as well as lipoprotein assembly. Autophagy directly targets apolipoprotein B-100 (apoB100), the structural protein component of very low-density lipoproteins (VLDLs), and further targets lipid droplets (LDs), the cellular storage for neutral lipids. Autophagy thus plays a complex and dual role in VLDL particle assembly by regulating apoB100 degradation as well as aiding the maturation of VLDL particles by hydrolyzing lipid from LDs. The purpose of this article is to review our current understanding of molecular and cellular mechanisms mediating authophagic control of hepatic lipid biogenesis and VLDL production as well as dysregulation in insulin resistance and dyslipidemia.