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J. Biol. Chem., Vol. 282, Issue 11, 8027-8035, March 16, 2007

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Attenuation of Adipocyte Triacylglycerol Hydrolase Activity Decreases Basal Fatty Acid Efflux^*

Enhui Wei¹, Wenhui Gao, and Richard Lehner, A Senior Scholar of the Alberta Heritage Foundation for Medical Research²

From the Departments of Pediatrics and Cell Biology, Canadian Institutes of Health Research Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada

Fatty acids released from adipose triacylglycerol stores by lipolysis provide vertebrates with an important source of energy. We investigated the role of microsomal triacylglycerol hydrolase (TGH) in the mobilization of adipocyte triacylglycerols through inactivation of the TGH activity by RNA interference or chemical inhibition. Attenuation of TGH activity resulted in decreased basal but not isoproterenol-stimulated efflux of fatty acids from 3T3-L1 adipocytes. Lack of TGH activity was accompanied by accumulation of cellular triacylglycerols and cholesteryl esters without any changes in the expression of enzymes catalyzing triacylglycerol synthesis (diacylglycerol acyltransferases 1 and 2) or degradation (adipose triglyceride lipase and hormone-sensitive lipase). Inhibition of TGH-mediated lipolysis also did not affect insulin-stimulated Glut4 translocation from intracellular compartments to the plasma membrane or glucose uptake into adipocytes. These data suggest that TGH plays a role in adipose tissue triacylglycerol metabolism and may be a suitable pharmacological target for lowering fatty acid efflux from adipose tissue without altering glucose import.

Received for publication, June 16, 2006 , and in revised form, November 13, 2006.

^* This work was supported Canadian Institutes of Health Research Grant MOP-69043. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by the Canadian Institutes of Health Research/Heart and Stroke Foundation of Canada/Industry Stroke, Cardiovascular, Obesity, Lipids, Atherosclerosis Research (SCOLAR) Training Program.

² To whom correspondence should be addressed: 328 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta T6G 2S2, Canada. Tel.: 780-492-2963; Fax: 780-492-3383; E-mail: richard.lehner{at}ualberta.ca.

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