title: Integrated Regulation of Hepatic Lipid and Glucose Metabolism by Adipose Triacylglycerol Lipase and FoxO Proteins.
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.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA; Medical Research Service, Jesse Brown VA Medical Center, Chicago, IL 60612, USA.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Zhang
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.
authors.forename: So Young
authors.initials: SY
authors.lastname: Bu
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.
authors.forename: Mara T
authors.initials: MT
authors.lastname: Mashek
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA; Medical Research Service, Jesse Brown VA Medical Center, Chicago, IL 60612, USA.
authors.forename: InSug
authors.initials: I
authors.lastname: O-Sullivan
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA; Medical Research Service, Jesse Brown VA Medical Center, Chicago, IL 60612, USA.
authors.forename: Zakaria
authors.initials: Z
authors.lastname: Sibai
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.
authors.forename: Salmaan A
authors.initials: SA
authors.lastname: Khan
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27710, USA; Department of Pharmacology, Duke University, Durham, NC 27710, USA; Department of Medicine, Duke University, Durham, NC 27710, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Ilkayeva
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27710, USA; Department of Pharmacology, Duke University, Durham, NC 27710, USA; Department of Medicine, Duke University, Durham, NC 27710, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
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
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA; Medical Research Service, Jesse Brown VA Medical Center, Chicago, IL 60612, USA. Electronic address: unterman@uic.edu.
authors.forename: Terry G
authors.initials: TG
authors.lastname: Unterman
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D000071161:Forkhead Box Protein O1 / Q000378:metabolism*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism*; D008297:Male; D008822:Mice, Transgenic; D008954:Models, Biological; D010084:Oxidation-Reduction
chemical_list: D018797:Cell Cycle Proteins; D005227:Fatty Acids; D000071161:Forkhead Box Protein O1; C467200:Foxo1 protein, mouse; C508072:G0S2 protein, mouse; D008049:Lipase; D005947:Glucose