Integrated Regulation of Hepatic Lipid and Glucose Metabolism by Adipose Triacylglycerol Lipase and FoxO Proteins.

Journal Article (Journal Article)

Metabolism is a highly integrated process that is coordinately regulated between tissues and within individual cells. FoxO proteins are major targets of insulin action and contribute to the regulation of gluconeogenesis, glycolysis, and lipogenesis in the liver. However, the mechanisms by which FoxO proteins exert these diverse effects in an integrated fashion remain poorly understood. We report that FoxO proteins also exert important effects on intrahepatic lipolysis and fatty acid oxidation via the regulation of adipose triacylglycerol lipase (ATGL), which mediates the first step in lipolysis, and its inhibitor, the G0/S1 switch 2 gene (G0S2). We also find that ATGL-dependent lipolysis plays a critical role in mediating diverse effects of FoxO proteins in the liver, including effects on gluconeogenic, glycolytic, and lipogenic gene expression and metabolism. These results indicate that intrahepatic lipolysis plays a critical role in mediating and integrating the regulation of glucose and lipid metabolism downstream of FoxO proteins.

Full Text

Duke Authors

Cited Authors

  • Zhang, W; Bu, SY; Mashek, MT; O-Sullivan, I; Sibai, Z; Khan, SA; Ilkayeva, O; Newgard, CB; Mashek, DG; Unterman, TG

Published Date

  • April 12, 2016

Published In

Volume / Issue

  • 15 / 2

Start / End Page

  • 349 - 359

PubMed ID

  • 27050511

Pubmed Central ID

  • PMC5346032

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2016.03.021


  • eng

Conference Location

  • United States