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

Aishwarya Sathyanarayan; Mara T Mashek; Douglas Mashek

doi:10.1016/j.celrep.2017.03.026

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

Aishwarya Sathyanarayan, Mara T Mashek, Douglas Mashek

Research output: Contribution to journal › Article › peer-review

260 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1-9
Number of pages	9
Journal	Cell reports
Volume	19
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2017.03.026
State	Published - Apr 4 2017

Bibliographical note

Funding Information:
This work was supported by grants from the NIH (DK090364) to D.G.M. and the Minnesota Obesity Center (NIH DK050456). The authors express their gratitude to Charles Najt for his expertise with LD isolations, as well as Codruta Vizoli and Mary McCourt for their excellent technical support. They also extend their gratitude to the staff at the University of Minnesota's Imaging Center, in particular, Grant Barthel and Alexander Cramer.

Publisher Copyright:
© 2017 The Author(s)

Keywords

ATGL
SIRT1
autophagy
fatty acid oxidation
lipid droplets
lipolysis
lipophagy
liver metabolism

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10.1016/j.celrep.2017.03.026

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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.",

keywords = "ATGL, SIRT1, autophagy, fatty acid oxidation, lipid droplets, lipolysis, lipophagy, liver metabolism",

author = "Aishwarya Sathyanarayan and Mashek, {Mara T} and Douglas Mashek",

note = "Funding Information: This work was supported by grants from the NIH (DK090364) to D.G.M. and the Minnesota Obesity Center (NIH DK050456). The authors express their gratitude to Charles Najt for his expertise with LD isolations, as well as Codruta Vizoli and Mary McCourt for their excellent technical support. They also extend their gratitude to the staff at the University of Minnesota's Imaging Center, in particular, Grant Barthel and Alexander Cramer. Publisher Copyright: {\textcopyright} 2017 The Author(s)",

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N1 - Funding Information: This work was supported by grants from the NIH (DK090364) to D.G.M. and the Minnesota Obesity Center (NIH DK050456). The authors express their gratitude to Charles Najt for his expertise with LD isolations, as well as Codruta Vizoli and Mary McCourt for their excellent technical support. They also extend their gratitude to the staff at the University of Minnesota's Imaging Center, in particular, Grant Barthel and Alexander Cramer. Publisher Copyright: © 2017 The Author(s)

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N2 - 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.

AB - 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.

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

Abstract

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

Abstract

Bibliographical note

Keywords

Publisher link

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Nikon A1si Spectral Confocal

University Imaging Centers

Cite this