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Am J Physiol Endocrinol Metab 293: E1736-E1745, 2007. First published September 11, 2007; doi:10.1152/ajpendo.00122.2007
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PPAR{gamma} regulates adipose triglyceride lipase in adipocytes in vitro and in vivo

Erin E. Kershaw,1 Michael Schupp,2 Hong-Ping Guan,2 Noah P. Gardner,1 Mitchell A. Lazar,2 and Jeffrey S. Flier1

1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts; and 2Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Submitted 23 February 2007 ; accepted in final form 8 September 2007

Peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) regulates adipocyte genes involved in adipogenesis and lipid metabolism and is the molecular target for thiazolidinedione (TZD) antidiabetic agents. Adipose triglyceride lipase (ATGL) is a recently described triglyceride-specific lipase that is induced during adipogenesis and remains highly expressed in mature adipocytes. This study evaluates the ability of PPAR{gamma} to directly regulate ATGL expression in adipocytes in vitro and in vivo. In fully differentiated 3T3-L1 adipocytes, ATGL mRNA and protein are increased by TZD and non-TZD PPAR{gamma} agonists in a dose- and time-dependent manner. Rosiglitazone-mediated induction of ATGL mRNA is rapid and is not inhibited by the protein synthesis inhibitor cycloheximide, indicating that intervening protein synthesis is not required for this effect. Rosiglitazone-mediated induction of ATGL mRNA and protein is inhibited by the PPAR{gamma}-specific antagonist GW-9662 and is also significantly reduced following siRNA-mediated knockdown of PPAR{gamma}, supporting the direct transcriptional regulation of ATGL by PPAR{gamma}. In vivo, ATGL mRNA and protein are increased by rosiglitazone treatment in white and brown adipose tissue of mice with and without obesity due to high-fat diet or leptin deficiency. Thus, PPAR{gamma} positively regulates ATGL mRNA and protein expression in mature adipocytes in vitro and in adipose tissue in vivo, suggesting a role for ATGL in mediating PPAR{gamma}'s effects on lipid metabolism.

peroxisome proliferator-activated receptor-{gamma}; thiazolidinediones; desnutrin; patatin-like phopholipase domain-containing protein A2; calcium-independent phospholipase A2-{zeta}


Address for reprint requests and other correspondence: E. E. Kershaw, Div. of Endocrinology and Metabolism, Dept. of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA, 02215 (e-mail: ekershaw{at}bidmc.harvard.edu)




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