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DOI: 10.2337/diabetes.55.01.06.db05-0982
© 2006 by the American Diabetes Association
Obesity Study |
Adipose Triglyceride Lipase
Function, Regulation by Insulin, and Comparison With Adiponutrin
1 Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
2 Joslin Diabetes Center, Boston, Massachusetts
Address correspondence and reprint requests to Erin E. Kershaw, MD, Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215. E-mail: ekershaw{at}bidmc.harvard.edu
Abbreviations:
ATGL, adipose triglyceride lipase; BAT, brown adipose tissue; FBS, fetal bovine serum; FIRKO, fat-specific insulin receptor knockout; HPRT, hypoxanthine guanine phosphoribosyl transferase; HSL, hormone-sensitive lipase; iPLA2, calcium-independent phospholipase A2; NEFA, nonesterified fatty acid; PGAT, perigonadal adipose tissue; PK, protein kinase; Q-PCR, quantitative real-time PCR; STZ, streptozotocin
Adipose triglyceride lipase (ATGL) is a recently described adipose-enriched protein with triglyceride-specific lipase activity. ATGL shares the greatest sequence homology with adiponutrin, a nutritionally regulated protein of unclear biological function. Here we present a functional analysis of ATGL and adiponutrin and describe their regulation by insulin. Retroviral-mediated overexpression of ATGL in 3T3-L1 adipocytes increased basal and isoproterenol-stimulated glycerol and nonesterified fatty acid (NEFA) release, whereas siRNA-mediated knockdown of ATGL had the opposite effect. In contrast, siRNA-mediated knockdown of adiponutrin in 3T3-L1 adipocytes had no effect on glycerol or NEFA release. In mice, both ATGL and adiponutrin are nutritionally regulated in adipose tissue, with ATGL being upregulated and adiponutrin being downregulated by fasting. In 3T3-L1 adipocytes, insulin decreased ATGL and increased adiponutrin expression in a dose- and time-dependent manner, suggesting that insulin directly mediates this nutritional regulation. In addition, adipose expression of ATGL was increased by insulin deficiency and decreased by insulin replacement in streptozotocin-induced diabetic mice and was increased in fat-specific insulin receptor knockout mice, whereas adiponutrin showed the opposite pattern. These data suggest that murine ATGL but not adiponutrin contributes to net adipocyte lipolysis and that ATGL and adiponutrin are oppositely regulated by insulin both in vitro and in vivo.
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