This Article Full Text Full Text (PDF) All Versions of this Article: 145/8/3925    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sell, H. Articles by Richard, D. Search for Related Content PubMed PubMed Citation Articles by Sell, H. Articles by Richard, D.

Peroxisome Proliferator-Activated Receptor Agonism Increases the Capacity for Sympathetically Mediated Thermogenesis in Lean and ob/ob Mice

Laval Hospital Research Center and Department of Anatomy and Physiology (H.S., P.S., J.L., Y.D., D.R.), School of Medicine, Laval University, Québec, Canada G1K 7P4; and Department of Metabolic Disorders (J.P.B., G.C.), Merck Research Laboratories, Rahway, New Jersey 07065

Address all correspondence and requests for reprints to: Professor Denis Richard, Department of Anatomy and Physiology, School of Medicine, Laval University, Québec, Canada G1K 7P4. E-mail: denis.richard{at}phs.ulaval.ca.

The nuclear receptor peroxisome proliferator-activated receptor (PPAR) modulates the expression of numerous genes involved in glucose and lipid homeostasis and plays a critical role in adipocyte differentiation. Expression of uncoupling protein (UCP)1, which is necessary for thermogenesis, is strongly stimulated by PPAR agonists but without an increase in energy expenditure. This study was designed to assess whether PPAR-induced UCP1 has any functional impact and, if so, whether it involves sympathetic activity. In a first phase, obese ob/ob C57BL/6J mice and lean controls were treated for 2 wk with the PPAR agonist [2-(2-[4-phenoxy-2-propylphenoxy]ethyl)indole-5-acetic acid] (COOH). COOH induced UCP1 expression in brown and white adipose tissues as well as that of other genes associated with substrate oxidation and thermogenesis. However, UCP1 induction did not increase energy expenditure, as assessed by indirect calorimetry and other energy balance measurements. In a second phase, mice received for an additional 2 wk a combination of COOH and the ß₃-adrenergic receptor (ß₃-AR) agonist CL-316243 to stimulate the adrenergic signaling pathway and assess whether COOH-induced UCP1 was physiologically functional. The ß₃-AR agonist stimulated thermogenesis in lean and ob/ob mice, an effect that was much stronger in COOH-pretreated mice, which exhibited lower respiratory quotient, higher oxygen consumption, and marked weight and fat mass loss, compared with mice not pretreated with COOH. These results demonstrate that PPAR agonism increases the thermogenic potential of white and brown adipose depots in lean and obese mice. This enhanced capacity leads to increased thermogenesis under ß-adrenergic stimulation, suggesting that the sympathetic drive is blunted by PPAR agonism.

This article has been cited by other articles:

				W. T. Festuccia, S. Oztezcan, M. Laplante, M. Berthiaume, C. Michel, S. Dohgu, R. G. Denis, M. N. Brito, N. A. Brito, D. S. Miller, et al. Peroxisome Proliferator-Activated Receptor-{gamma}-Mediated Positive Energy Balance in the Rat Is Associated with Reduced Sympathetic Drive to Adipose Tissues and Thyroid Status Endocrinology, May 1, 2008; 149(5): 2121 - 2130. [Abstract] [Full Text] [PDF]

				S. Sena, I. R. Rasmussen, A. R. Wende, A. P. McQueen, H. A. Theobald, N. Wilde, R. O. Pereira, S. E. Litwin, J. P. Berger, and E. D. Abel Cardiac Hypertrophy Caused by Peroxisome Proliferator- Activated Receptor-{gamma} Agonist Treatment Occurs Independently of Changes in Myocardial Insulin Signaling Endocrinology, December 1, 2007; 148(12): 6047 - 6053. [Abstract] [Full Text] [PDF]

				I. Bogacka, T. W. Gettys, L. de Jonge, T. Nguyen, J. M. Smith, H. Xie, F. Greenway, and S. R. Smith The Effect of {beta}-Adrenergic and Peroxisome Proliferator-Activated Receptor-{gamma} Stimulation on Target Genes Related to Lipid Metabolism in Human Subcutaneous Adipose Tissue Diabetes Care, May 1, 2007; 30(5): 1179 - 1186. [Abstract] [Full Text] [PDF]

				M. Laplante, W. T. Festuccia, G. Soucy, Y. Gelinas, J. Lalonde, and Y. Deshaies Involvement of adipose tissues in the early hypolipidemic action of PPAR{gamma} agonism in the rat Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1408 - R1417. [Abstract] [Full Text] [PDF]

				S. L. Gray, E. Dalla Nora, E. C. Backlund, M. Manieri, S. Virtue, R. C. Noland, S. O'Rahilly, R. N. Cortright, S. Cinti, B. Cannon, et al. Decreased Brown Adipocyte Recruitment and Thermogenic Capacity in Mice with Impaired Peroxisome Proliferator-Activated Receptor (P465L PPAR{gamma}) Function Endocrinology, December 1, 2006; 147(12): 5708 - 5714. [Abstract] [Full Text] [PDF]

				V. Golozoubova, B. Cannon, and J. Nedergaard UCP1 is essential for adaptive adrenergic nonshivering thermogenesis Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E350 - E357. [Abstract] [Full Text] [PDF]

				E. Hondares, O. Mora, P. Yubero, M. R. de la Concepcion, R. Iglesias, M. Giralt, and F. Villarroya Thiazolidinediones and Rexinoids Induce Peroxisome Proliferator-Activated Receptor-Coactivator (PGC)-1{alpha} Gene Transcription: An Autoregulatory Loop Controls PGC-1{alpha} Expression in Adipocytes via Peroxisome Proliferator-Activated Receptor-{gamma} Coactivation Endocrinology, June 1, 2006; 147(6): 2829 - 2838. [Abstract] [Full Text] [PDF]

				I. Bogacka, B. Ukropcova, M. McNeil, J. M. Gimble, and S. R. Smith Structural and Functional Consequences of Mitochondrial Biogenesis in Human Adipocytes in Vitro J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6650 - 6656. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, J. N. Roemmich, E. J. Richmond, A. D. Rogol, J. C. Lovejoy, M. Sheffield-Moore, N. Mauras, and C. Y. Bowers Endocrine Control of Body Composition in Infancy, Childhood, and Puberty Endocr. Rev., February 1, 2005; 26(1): 114 - 146. [Abstract] [Full Text] [PDF]