title: ATGL Promotes Autophagy/Lipophagy via SIRT1 to Control Hepatic Lipid Droplet Catabolism.
abstract: 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.
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN 55108, USA.
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Sathyanarayan
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Mara T
authors.initials: MT
authors.lastname: Mashek
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: dmashek@umn.edu.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Mashek
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001343:Autophagy; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D066292:Lipid Droplets / Q000737:chemistry / Q000378:metabolism*; D050356:Lipid Metabolism; D008066:Lipolysis; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D010084:Oxidation-Reduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D000217:Acyltransferases
chemical_list: D005227:Fatty Acids; D008049:Lipase; D056564:Sirtuin 1; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases; C470545:Sirt1 protein, mouse
keywords: ATGL; SIRT1; autophagy; fatty acid oxidation; lipid droplets; lipolysis; lipophagy; liver metabolism