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 language | English (US) |
|---|---|
| Pages (from-to) | 349-359 |
| Number of pages | 11 |
| Journal | Cell reports |
| Volume | 15 |
| Issue number | 2 |
| DOIs | |
| State | Published - Apr 12 2016 |
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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 journal › Article
}
TY - JOUR
T1 - Integrated Regulation of Hepatic Lipid and Glucose Metabolism by Adipose Triacylglycerol Lipase and FoxO Proteins
AU - Zhang, Wenwei
AU - Bu, So Young
AU - Mashek, Mara T.
AU - O-Sullivan, In Sug
AU - Sibai, Zakaria
AU - Khan, Salmaan A.
AU - Ilkayeva, Olga
AU - Newgard, Christopher B.
AU - Mashek, Douglas G.
AU - Unterman, Terry G.
PY - 2016/4/12
Y1 - 2016/4/12
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84962082073&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2016.03.021
DO - 10.1016/j.celrep.2016.03.021
M3 - Article
C2 - 27050511
AN - SCOPUS:84962082073
VL - 15
SP - 349
EP - 359
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 2
ER -