HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) 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 Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Edvardsson, U. Articles by Dahllöf, B. Search for Related Content PubMed PubMed Citation Articles by Edvardsson, U. Articles by Dahllöf, B. Social Bookmarking                      What's this?

The Journal of Lipid Research, Vol. 40, 1177-1184, July 1999
Copyright © 1999 by Lipid Research, Inc.

Original Article

Rosiglitazone (BRL49653), a PPAR-selective agonist, causes peroxisome proliferator-like liver effects in obese mice

Correspondence to: Björn Dahllöf

The PPAR (peroxisome proliferator activated receptor) transcription factors are ligand-activated nuclear receptors that regulate genes involved in lipid metabolism and homeostasis. PPAR is preferentially expressed in liver and PPAR preferentially in adipose tissue. Activation of PPAR leads to peroxisome proliferation and increased ß-oxidation of fatty acids in rodents. PPAR-activation leads to adipocyte differentiation and improved insulin signaling of mature adipocytes. Both PPAR receptors are believed to be functional targets for treatment of hyperlipidemia in man. We have treated obese diabetic mice (ob/ob), which have highly elevated levels of plasma triglycerides, glucose and insulin, for 1 week with WY14,643 (180 µmol/kg/day), a selective PPAR agonist, or rosiglitazone (BRL49653; 2.5 µmol/kg/day), a selective PPAR agonist. The doses used produce a similar therapeutic effect in both treatment groups (lowering of triglycerides and glucose). High resolution two-dimensional gel electrophoresis of livers showed that WY14,643 and rosiglitazone both produced changes in expression pattern of many proteins involved in peroxisomal fatty acid ß-oxidation. However, similar experiments performed in lean mice showed significant up-regulation of these proteins only with WY14,643 treatment. Furthermore, the proteins up-regulated by the drugs in obese mice had a higher basal expression in obese controls compared to the lean littermates. Liver PPAR mRNA levels were determined and we observed that PPAR2 mRNA levels were elevated in obese mice compared to lean littermates. As PPAR and PPAR recognize similar DNA response elements, it is likely that the effects of rosiglitazone on PPAR responsive genes in livers of the ob/ob mice are mediated by PPAR2. — Edvardsson, U., M. Bergström, M. Alexandersson, K. Bamberg, B. Ljung, and B. Dahllöf. Rosiglitazone (BRL49653), a PPAR-selective agonist, causes peroxisome proliferator-like liver effects in obese mice. J. Lipid Res. 1999. 40: 1177;–1184.

Supplementary key words: BRL49653, WY14,643, peroxisome proliferation, PPAR, proteomics, ob/ob, obese mice, insulin resistance, two-dimensional gel electrophoresis

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Beysen, E. J. Murphy, H. Nagaraja, M. Decaris, T. Riiff, A. Fong, M. K. Hellerstein, and P. J. Boyle A pilot study of the effects of pioglitazone and rosiglitazone on de novo lipogenesis in type 2 diabetes J. Lipid Res., December 1, 2008; 49(12): 2657 - 2663. [Abstract] [Full Text] [PDF]

				M. Adiels, S.-O. Olofsson, M.-R. Taskinen, and J. Boren Overproduction of Very Low-Density Lipoproteins Is the Hallmark of the Dyslipidemia in the Metabolic Syndrome Arterioscler. Thromb. Vasc. Biol., July 1, 2008; 28(7): 1225 - 1236. [Abstract] [Full Text] [PDF]

				Y. Wang, K. S. L. Lam, J. B. B. Lam, M. C. Lam, P. T. Y. Leung, M. Zhou, and A. Xu Overexpression of Angiopoietin-Like Protein 4 Alters Mitochondria Activities and Modulates Methionine Metabolic Cycle in the Liver Tissues of db/db Diabetic Mice Mol. Endocrinol., April 1, 2007; 21(4): 972 - 986. [Abstract] [Full Text] [PDF]

				B. Desvergne, L. Michalik, and W. Wahli Transcriptional Regulation of Metabolism Physiol Rev, April 1, 2006; 86(2): 465 - 514. [Abstract] [Full Text] [PDF]

				D. Linden, L. William-Olsson, A. Ahnmark, K. Ekroos, C. Hallberg, H. P. Sjogren, B. Becker, L. Svensson, J. C. Clapham, J. Oscarsson, et al. Liver-directed overexpression of mitochondrial glycerol-3-phosphate acyltransferase results in hepatic steatosis, increased triacylglycerol secretion and reduced fatty acid oxidation FASEB J, March 1, 2006; 20(3): 434 - 443. [Abstract] [Full Text] [PDF]

				N. D. Oakes, P. Thalen, T. Hultstrand, S. Jacinto, G. Camejo, B. Wallin, and B. Ljung Tesaglitazar, a dual PPAR{alpha}/{gamma} agonist, ameliorates glucose and lipid intolerance in obese Zucker rats Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2005; 289(4): R938 - R946. [Abstract] [Full Text] [PDF]

				C. Sharma, A. Pradeep, L. Wong, A. Rana, and B. Rana Peroxisome Proliferator-activated Receptor {gamma} Activation Can Regulate {beta}-Catenin Levels via a Proteasome-mediated and Adenomatous Polyposis Coli-independent Pathway J. Biol. Chem., August 20, 2004; 279(34): 35583 - 35594. [Abstract] [Full Text] [PDF]

				M. Tiikkainen, A.-M. Hakkinen, E. Korsheninnikova, T. Nyman, S. Makimattila, and H. Yki-Jarvinen Effects of Rosiglitazone and Metformin on Liver Fat Content, Hepatic Insulin Resistance, Insulin Clearance, and Gene Expression in Adipose Tissue in Patients With Type 2 Diabetes Diabetes, August 1, 2004; 53(8): 2169 - 2176. [Abstract] [Full Text] [PDF]

				P. Mohanty, A. Aljada, H. Ghanim, D. Hofmeyer, D. Tripathy, T. Syed, W. Al-Haddad, S. Dhindsa, and P. Dandona Evidence for a Potent Antiinflammatory Effect of Rosiglitazone J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2728 - 2735. [Abstract] [Full Text] [PDF]

				M. Muurling, A. M. van den Hoek, R. P. Mensink, H. Pijl, J. A. Romijn, L. M. Havekes, and P. J. Voshol Overexpression of APOC1 in obob mice leads to hepatic steatosis and severe hepatic insulin resistance J. Lipid Res., January 1, 2004; 45(1): 9 - 16. [Abstract] [Full Text] [PDF]

				O. Gavrilova, M. Haluzik, K. Matsusue, J. J. Cutson, L. Johnson, K. R. Dietz, C. J. Nicol, C. Vinson, F. J. Gonzalez, and M. L. Reitman Liver Peroxisome Proliferator-activated Receptor {gamma} Contributes to Hepatic Steatosis, Triglyceride Clearance, and Regulation of Body Fat Mass J. Biol. Chem., September 5, 2003; 278(36): 34268 - 34276. [Abstract] [Full Text] [PDF]

				R. J. Gum, L. L. Gaede, M. A. Heindel, J. F. Waring, J. M. Trevillyan, B. A. Zinker, M. E. Stark, D. Wilcox, M. R. Jirousek, C. M. Rondinone, et al. Antisense Protein Tyrosine Phosphatase 1B Reverses Activation of p38 Mitogen-Activated Protein Kinase in Liver of ob/ob Mice Mol. Endocrinol., June 1, 2003; 17(6): 1131 - 1143. [Abstract] [Full Text] [PDF]

				M. Korc Diabetes Mellitus in the Era of Proteomics Mol. Cell. Proteomics, June 1, 2003; 2(6): 399 - 404. [Full Text] [PDF]

				A. Gauthier, G. Vassiliou, F. Benoist, and R. McPherson Adipocyte Low Density Lipoprotein Receptor-related Protein Gene Expression and Function Is Regulated by Peroxisome Proliferator-activated Receptor gamma J. Biol. Chem., March 28, 2003; 278(14): 11945 - 11953. [Abstract] [Full Text] [PDF]

				B. Ljung, K. Bamberg, B. Dahllof, A. Kjellstedt, N. D. Oakes, J. Ostling, L. Svensson, and G. Camejo AZ 242, a novel PPAR{alpha}/{gamma} agonist with beneficial effects on insulin resistance and carbohydrate and lipid metabolism in ob/ob mice and obese Zucker rats J. Lipid Res., November 1, 2002; 43(11): 1855 - 1863. [Abstract] [Full Text] [PDF]

				A. Carpentier, C. Taghibiglou, N. Leung, L. Szeto, S. C. Van Iderstine, K. D. Uffelman, R. Buckingham, K. Adeli, and G. F. Lewis Ameliorated Hepatic Insulin Resistance Is Associated with Normalization of Microsomal Triglyceride Transfer Protein Expression and Reduction in Very Low Density Lipoprotein Assembly and Secretion in the Fructose-fed Hamster J. Biol. Chem., August 2, 2002; 277(32): 28795 - 28802. [Abstract] [Full Text] [PDF]

				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]

				J. G. DeLuca, T. W. Doebber, L. J. Kelly, R. K. Kemp, S. Molon-Noblot, S. P. Sahoo, J. Ventre, M. S. Wu, J. M. Peters, F. J. Gonzalez, et al. Evidence for Peroxisome Proliferator-Activated Receptor (PPAR)alpha -Independent Peroxisome Proliferation: Effects of PPARgamma /delta -Specific Agonists in PPARalpha -Null Mice Mol. Pharmacol., September 1, 2000; 58(3): 470 - 476. [Abstract] [Full Text]

				M.-H. Hsu, U. Savas, K. J. Griffin, and E. F. Johnson Identification of Peroxisome Proliferator-responsive Human Genes by Elevated Expression of the Peroxisome Proliferator-activated Receptor alpha in HepG2 Cells J. Biol. Chem., July 20, 2001; 276(30): 27950 - 27958. [Abstract] [Full Text] [PDF]