This Article Full Text Full Text (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 Camirand, A. Articles by Silva, J. E. Search for Related Content PubMed PubMed Citation Articles by Camirand, A. Articles by Silva, J. E.

Thiazolidinediones Stimulate Uncoupling Protein-2 Expression in Cell Lines Representing White and Brown Adipose Tissues and Skeletal Muscle

Division of Endocrinology and Metabolism, Lady Davis Institute at Jewish General Hospital, McGill University, Montréal, Québec H3T 1E2, Canada

Address all correspondence and requests for reprints to: J. Enrique Silva, M.D., Jewish General Hospital, Division of Endocrinology, Room E-163, 3755 Cote-St.-Catherine Road, Montréal, Québec H3T 1E2, Canada.

Thiazolidinediones (TZD) are PPARy ligands that sensitize tissues to insulin. A cDNA encoding a mitochondrial protein likely to act as uncoupler (uncoupling protein 2, UCP2) has been recently cloned. Since TZD have been reported to increase energy expenditure in animals, we have examined the effects of these drugs on the expression of UCP2 mRNA in cell lines representing white (3T3-L1 and 3T3-F442A) and brown (HIB-1B) adipose tissues and skeletal muscle (L6). Northern blots probed with a mouse UCP2 full-length cDNA showed a mRNA of 1.6 kb both in tissues and the aforementioned cells lines. Within 4 h of exposing these cells to 30 µM darglitazone, there was an increase in UCP2 mRNA which reached a plateau of 5–10 times the basal in about 8 h. In all cells TZDs (darglitazone, troglitazone) were more active than the predominantly PPAR ligands WY-14,613 and clofibrate, or the non-selective ligand linoleic acid. These results indicate that TZDs can stimulate the expression of UCP2 gene probably via PPARy and hence have the potential to increase energy expenditure in adult humans, in whom UCP2 is expressed ubiquitously.

This article has been cited by other articles:

				J. Bispham, D. S. Gardner, M. G. Gnanalingham, T. Stephenson, M. E. Symonds, and H. Budge Maternal Nutritional Programming of Fetal Adipose Tissue Development: Differential Effects on Messenger Ribonucleic Acid Abundance for Uncoupling Proteins and Peroxisome Proliferator-Activated and Prolactin Receptors Endocrinology, September 1, 2005; 146(9): 3943 - 3949. [Abstract] [Full Text] [PDF]

				M. D. Aleo, G. R. Lundeen, D. K. Blackwell, W. M. Smith, G. L. Coleman, S. W. Stadnicki, and W. M. Kluwe Mechanism and Implications of Brown Adipose Tissue Proliferation in Rats and Monkeys Treated with the Thiazolidinedione Darglitazone, a Potent Peroxisome Proliferator-Activated Receptor-{gamma} Agonist J. Pharmacol. Exp. Ther., June 1, 2003; 305(3): 1173 - 1182. [Abstract] [Full Text] [PDF]

				K. Eto, T. Yamashita, J. Matsui, Y. Terauchi, M. Noda, and T. Kadowaki Genetic Manipulations of Fatty Acid Metabolism in {beta}-Cells Are Associated With Dysregulated Insulin Secretion Diabetes, December 1, 2002; 51(90003): S414 - 420. [Abstract] [Full Text] [PDF]

				G. Argyropoulos and M.-E. Harper Molecular Biology of Thermoregulation: Invited Review: Uncoupling proteins and thermoregulation J Appl Physiol, May 1, 2002; 92(5): 2187 - 2198. [Abstract] [Full Text] [PDF]

				S. Collins, W. Cao, K. W. Daniel, T. M. Dixon, A. V. Medvedev, H. Onuma, and R. Surwit Adrenoceptors, Uncoupling Proteins, and Energy Expenditure Experimental Biology and Medicine, December 1, 2001; 226(11): 982 - 990. [Abstract] [Full Text] [PDF]

				M. B. Armstrong and H. C. Towle Polyunsaturated fatty acids stimulate hepatic UCP-2 expression via a PPARalpha -mediated pathway Am J Physiol Endocrinol Metab, December 1, 2001; 281(6): E1197 - E1204. [Abstract] [Full Text] [PDF]

				N. Lameloise, P. Muzzin, M. Prentki, and F. Assimacopoulos-Jeannet Uncoupling Protein 2: A Possible Link Between Fatty Acid Excess and Impaired Glucose-Induced Insulin Secretion? Diabetes, April 1, 2001; 50(4): 803 - 809. [Abstract] [Full Text]

				R. A. Memon, L. H. Tecott, K. Nonogaki, A. Beigneux, A. H. Moser, C. Grunfeld, and K. R. Feingold Up-Regulation of Peroxisome Proliferator-Activated Receptors (PPAR-{alpha}) and PPAR-{gamma} Messenger Ribonucleic Acid Expression in the Liver in Murine Obesity: Troglitazone Induces Expression of PPAR-{gamma}-Responsive Adipose Tissue-Specific Genes in the Liver of Obese Diabetic Mice Endocrinology, November 1, 2000; 141(11): 4021 - 4031. [Abstract] [Full Text] [PDF]

				X. X. Yu, J. L. Barger, B. B. Boyer, M. D. Brand, G. Pan, and S. H. Adams Impact of endotoxin on UCP homolog mRNA abundance, thermoregulation, and mitochondrial proton leak kinetics Am J Physiol Endocrinol Metab, August 1, 2000; 279(2): E433 - E446. [Abstract] [Full Text] [PDF]

				M. Boivin, A. Camirand, F. Carli, L. J. Hoffer, and J. E. Silva Uncoupling Protein-2 and -3 Messenger Ribonucleic Acids in Adipose Tissue and Skeletal Muscle of Healthy Males: Variability, Factors Affecting Expression, and Relation to Measures of Metabolic Rate J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1975 - 1983. [Abstract] [Full Text]

				K. A. J. M. VAN DER LEE, P. H. M. WILLEMSEN, G. J. VAN DER VUSSE, and M. VAN BILSEN Effects of fatty acids on uncoupling protein-2 expression in the rat heart FASEB J, March 1, 2000; 14(3): 495 - 502. [Abstract] [Full Text]

				H. Vidal, D. Langin, F. Andreelli, L. Millet, D. Larrouy, and M. Laville Lack of skeletal muscle uncoupling protein 2 and 3 mRNA induction during fasting in type-2 diabetic subjects Am J Physiol Endocrinol Metab, November 1, 1999; 277(5): E830 - E837. [Abstract] [Full Text] [PDF]

				L. Poretsky, N. A. Cataldo, Z. Rosenwaks, and L. C. Giudice The Insulin-Related Ovarian Regulatory System in Health and Disease Endocr. Rev., August 1, 1999; 20(4): 535 - 582. [Abstract] [Full Text] [PDF]

				H. Yang, J. M. Egan, B. D. Rodgers, M. Bernier, and C. Montrose-Rafizadeh Differential Expression of a Novel Seven Transmembrane Domain Protein in Epididymal Fat from Aged and Diabetic Mice Endocrinology, June 1, 1999; 140(6): 2859 - 2867. [Abstract] [Full Text]

				R. C. Cooksey, L. F. Hebert Jr., J.-H. Zhu, P. Wofford, W. T. Garvey, and D. A. McClain Mechanism of Hexosamine-Induced Insulin Resistance in Transgenic Mice Overexpressing Glutamine:Fructose-6-Phosphate Amidotransferase: Decreased Glucose Transporter GLUT4 Translocation and Reversal by Treatment with Thiazolidinedione Endocrinology, March 1, 1999; 140(3): 1151 - 1157. [Abstract] [Full Text]

				L. J. Kelly, P. P. Vicario, G. M. Thompson, M. R. Candelore, T. W. Doebber, J. Ventre, M. S. Wu, R. Meurer, M. J. Forrest, M. W. Conner, et al. Peroxisome Proliferator-Activated Receptors {gamma} and {alpha} Mediate in Vivo Regulation of Uncoupling Protein (UCP-1, UCP-2, UCP-3) Gene Expression Endocrinology, December 1, 1998; 139(12): 4920 - 4927. [Abstract] [Full Text] [PDF]

				E. Chevillotte, J. Rieusset, M. Roques, M. Desage, and H. Vidal The Regulation of Uncoupling Protein-2 Gene Expression by omega -6 Polyunsaturated Fatty Acids in Human Skeletal Muscle Cells Involves Multiple Pathways, Including the Nuclear Receptor Peroxisome Proliferator-activated Receptor beta J. Biol. Chem., March 30, 2001; 276(14): 10853 - 10860. [Abstract] [Full Text] [PDF]

				A. V. Medvedev, S. K. Snedden, S. Raimbault, D. Ricquier, and S. Collins Transcriptional Regulation of the Mouse Uncoupling Protein-2 Gene. DOUBLE E-BOX MOTIF IS REQUIRED FOR PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-gamma -DEPENDENT ACTIVATION J. Biol. Chem., March 30, 2001; 276(14): 10817 - 10823. [Abstract] [Full Text] [PDF]