Title: Complex role of autophagy in regulation of hepatic lipid and lipoprotein metabolism
Authors: Mostafa Zamani1,3, Jennifer Taher1,2, Khosrow Adeli1,2,3
Institutions: 1Molecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; 2Department of Laboratory Medicine and Pathobiology, University of Toronto, ON M5G 0A4, Canada;3Department of Biochemistry, University of Toronto, ON M5G 0A4, Canada.
Abstract: 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.
Keywords: autophagy, lipophagy, lipid droplets, apolipoprotein B-100, VLDL, dyslipidemia, hepatic steatosis
Full Text: PDF JBR-2015-0137
J Biomed Res published on March 03rd, 2016, doi: 10.7555/JBR.30.20150137