ATGL Promotes Autophagy/Lipophagy via SIRT1 to Control Hepatic Lipid Droplet Catabolism

Publication date: 4 April 2017
Source:Cell Reports, Volume 19, Issue 1
Author(s): Aishwarya Sathyanarayan, Mara T. Mashek, Douglas G. Mashek
Hepatic lipid droplet (LD) catabolism is thought to occur via cytosolic lipases such as adipose triglyceride lipase (ATGL) or through autophagy of LDs, a process known as lipophagy. We tested the potential interplay between these metabolic processes and its effects on hepatic lipid metabolism. We show that hepatic ATGL is both necessary and sufficient to induce both autophagy and lipophagy. Moreover, lipophagy is required for ATGL to promote LD catabolism and the subsequent oxidation of hydrolyzed fatty acids (FAs). Following previous work showing that ATGL promotes sirtuin 1 (SIRT1) activity, studies in liver-specific SIRT1^−/− mice and in primary hepatocytes reveal that SIRT1 is required for ATGL-mediated induction of autophagy and lipophagy. Taken together, these studies show that ATGL-mediated signaling via SIRT1 promotes autophagy/lipophagy as a primary means to control hepatic LD catabolism and FA oxidation.

Graphical abstract

Teaser

Sathyanarayan et al. find that hepatic ATGL signals through SIRT1 to promote autophagy/lipophagy and coordinate lipid droplet catabolism. Functional lipophagy is required for hepatic triglyceride catabolism and fatty acid oxidation.


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