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

Wenwei Zhang, So Young Bu, Mara T. Mashek, In Sug O-Sullivan, Zakaria Sibai, Salmaan A. Khan, Olga Ilkayeva, Christopher B. Newgard, Douglas G. Mashek, Terry G. Unterman

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)349-359
Number of pages11
JournalCell reports
Volume15
Issue number2
DOIs
StatePublished - Apr 12 2016

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Lipase
Lipid Metabolism
Metabolism
Lipolysis
Lipids
Glucose
Liver
Proteins
Switch Genes
Lipogenesis
Gluconeogenesis
Glycolysis
Gene expression
Fatty Acids
Genes
Switches
Insulin
Tissue
Gene Expression
Oxidation

Cite this

Integrated Regulation of Hepatic Lipid and Glucose Metabolism by Adipose Triacylglycerol Lipase and FoxO Proteins. / Zhang, Wenwei; Bu, So Young; Mashek, Mara T.; O-Sullivan, In Sug; Sibai, Zakaria; Khan, Salmaan A.; Ilkayeva, Olga; Newgard, Christopher B.; Mashek, Douglas G.; Unterman, Terry G.

In: Cell reports, Vol. 15, No. 2, 12.04.2016, p. 349-359.

Research output: Contribution to journalArticle

Zhang, W, Bu, SY, Mashek, MT, O-Sullivan, IS, Sibai, Z, Khan, SA, Ilkayeva, O, Newgard, CB, Mashek, DG & Unterman, TG 2016, 'Integrated Regulation of Hepatic Lipid and Glucose Metabolism by Adipose Triacylglycerol Lipase and FoxO Proteins', Cell reports, vol. 15, no. 2, pp. 349-359. https://doi.org/10.1016/j.celrep.2016.03.021
Zhang, Wenwei ; Bu, So Young ; Mashek, Mara T. ; O-Sullivan, In Sug ; Sibai, Zakaria ; Khan, Salmaan A. ; Ilkayeva, Olga ; Newgard, Christopher B. ; Mashek, Douglas G. ; Unterman, Terry G. / Integrated Regulation of Hepatic Lipid and Glucose Metabolism by Adipose Triacylglycerol Lipase and FoxO Proteins. In: Cell reports. 2016 ; Vol. 15, No. 2. pp. 349-359.
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