Integrated Regulation of Hepatic Lipid and Glucose Metabolism by Adipose Triacylglycerol Lipase and FoxO Proteins
| Autor: | So Young Bu, In Sug O-Sullivan, Salmaan A. Khan, Wenwei Zhang, Douglas G. Mashek, Zakaria Sibai, Christopher B. Newgard, Terry G. Unterman, Olga Ilkayeva, Mara T. Mashek |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine endocrine system Adipose tissue Cell Cycle Proteins Mice Transgenic Biology Carbohydrate metabolism Models Biological Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Animals Homeostasis Humans Lipolysis Glycolysis lcsh:QH301-705.5 Beta oxidation Forkhead Box Protein O1 Lipogenesis fungi Fatty Acids Lipid metabolism Lipase Lipid Metabolism Glucose 030104 developmental biology lcsh:Biology (General) Adipose Tissue Gene Expression Regulation Liver Biochemistry Gluconeogenesis 030220 oncology & carcinogenesis embryonic structures Hepatocytes biological phenomena cell phenomena and immunity Oxidation-Reduction hormones hormone substitutes and hormone antagonists |
| Zdroj: | Cell Reports, Vol 15, Iss 2, Pp 349-359 (2016) |
| ISSN: | 2211-1247 |
| Popis: | FoxO proteins are major targets of insulin action. Adipose triacylglycerol (TAG) lipase mediates the first step in TAG hydrolysis and FoxO1 stimulates ATGL expression in adipose tissue. Here, we report that FoxO1 also stimulates ATGL and suppresses expression of its inhibitor, the G0/G1 switch gene protein 2 (G0S2), in the liver. Studies in FoxO transgenic and knockout mice and hepatocytes show that FoxO proteins mediate effects of insulin on ATGL and G0S2 expression. Further, ATGL-dependent lipolysis mediates effects of FoxOs on glycolytic, lipogenic and gluconeogenic gene expression and metabolism, including fatty acid oxidation, which is required for effects of FoxO1 on glucose homeostasis. These results reveal that ATGL-dependent lipolysis and fatty acid oxidation play a critical role in integrating the regulation of glucose and lipid metabolism downstream from FoxO proteins in the liver, and suggest that targeting ATGL-dependent lipolysis and its downstream effectors may provide an effective strategy for improving the treatment of patients with diabetes and hepatic insulin resistance. |
| Databáze: | OpenAIRE |
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