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Papers In Press, published online ahead of print June 1, 2009
J. Lipid Res., doi:10.1194/jlr.M800620-JLR200

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Journal of Lipid Research, Vol. 50, 1185-1194, June 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Depot-specific effects of the PPAR agonist rosiglitazone on adipose tissue glucose uptake and metabolism

William T. Festuccia^*, Pierre-Gilles Blanchard^*, Véronique Turcotte^*, Mathieu Laplante, Meltem Sariahmetoglu, David N. Brindley and Yves Deshaies^1,*

^* Laval Hospital Research Center and Department of Anatomy and Physiology, Faculty of Medicine, Laval University, Quebec, Canada G1V 4G5
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142
Signal Transduction Research Group, Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of one figure and one table.

This work was supported by a grant from the Canadian Institutes of Health Research to Y.D. and from the Heart and Stroke Foundation of Canada to D.N.B. P-G.B. was the recipient of a Frederick Banting and Charles Best Canada Graduate Scholarships, Doctoral Award from the Canadian Institutes of Health Research.

Published, JLR Papers in Press, February 5, 2009.

¹ To whom correspondence should be addressed. e-mail: yves.deshaies{at}phs.ulaval.ca

We investigated mechanisms whereby peroxisome proliferator-activated receptor (PPAR) agonism redistributes lipid from visceral (VF) toward subcutaneous fat (SF) by studying the impact of PPAR activation on VF and SF glucose uptake and metabolism, lipogenesis, and enzymes involved in triacylglycerol (TAG) synthesis. VF (retroperitoneal) and SF (inguinal) of rats treated or not for 7 days with rosiglitazone (15 mg/kg/day) were evaluated in vivo for glucose uptake and lipogenesis and in vitro for glucose metabolism, gene expression, and activities of glycerolphosphate acyltransferase (GPAT), phosphatidate phosphatase-1 (or lipin-1), and diacylglycerol acyltransferase. Rosiglitazone increased SF glucose uptake, GLUT4 mRNA, and insulin-stimulated glucose oxidation, conversion to lactate, glycogen, and the glycerol and fatty acid components of TAG. In VF, only glucose incorporation into TAG-glycerol was stimulated by rosiglitazone and less so than in SF (1.5- vs. 3-fold). mRNA levels of proteins involved in glycolysis, Krebs cycle, glycogen synthesis, and lipogenesis were markedly upregulated by rosiglitazone in SF and again less so in VF. Rosiglitazone activated TAG-glycerol synthesis in vivo (2.8- vs. 1.9-fold) and lipin activity (4.6- vs. 1.5-fold) more strongly in SF than VF, whereas GPAT activity was increased similarly in both depots. The preferential increase in glucose uptake and intracellular metabolism in SF contributes to the PPAR-mediated redistribution of TAG from VF to SF, which in turn favors global insulin sensitization.

Supplementary key words glucose oxidation • lipogenesis • glycerol 3-phosphate acyltransferase • lipin • diacylglycerol acyltransferase • visceral fat • subcutaneous fat

Abbreviations: CIDEC, cell death-inducing DNA fragmentation factor--like effector; DGAT, diacylglycerol acyltransferase; G6PDH, glucose 6-phosphate dehydrogenase; GLUT, glucose transporter; GPAT, glycerol 3-phosphate acyltransferase; GyS2, glycogen synthase 2; ME, malic enzyme; NEFA, nonesterified fatty acid; PAP-1, phosphatidate phosphatase-1; PEPCK, phosphoenolpyruvate carboxykinase; PPAR, peroxisome proliferator-activated receptor ; SF, subcutaneous fat; SREBP1, sterol regulatory binding protein 1; TAG, triacylglycerol; UDPG-PPL, UDP-glucose pyrophosphorylase; VF, visceral fat; WAT, white adipose tissue

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