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PPAR Research
Volume 2010, Article ID 679184, 17 pages
Research Article

Coordinate Transcriptomic and Metabolomic Effects of the Insulin Sensitizer Rosiglitazone on Fundamental Metabolic Pathways in Liver, Soleus Muscle, and Adipose Tissue in Diabetic db/db Mice

1Division of Molecular Pharmacology and Pathophysiology, Institut de Recherches Servier, 125 Chemin de Ronde, 78290 Croissy-sur-Seine, France
2Department of Biostatistics, Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, France
3Metabolisme BA, Technologie Servier, 5 rue Bel Air, 45000 Orleans, France
4Division of Diabetes Metabolic Diseases Research, Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, France

Received 29 April 2010; Revised 16 July 2010; Accepted 11 August 2010

Academic Editor: Chih-Hao Lee

Copyright © 2010 Sabrina Le Bouter et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Rosiglitazone (RSG), developed for the treatment of type 2 diabetes mellitus, is known to have potent effects on carbohydrate and lipid metabolism leading to the improvement of insulin sensitivity in target tissues. To further assess the capacity of RSG to normalize gene expression in insulin-sensitive tissues, we compared groups of 18-day-treated db/db mice with increasing oral doses of RSG (10, 30, and 100 mg/kg/d) with untreated non-diabetic littermates (db/+). For this aim, transcriptional changes were measured in liver, inguinal adipose tissue (IAT) and soleus muscle using microarrays and real-time PCR. In parallel, targeted metabolomic assessment of lipids (triglycerides (TGs) and free fatty acids (FFAs)) in plasma and tissues was performed by UPLC-MS methods. Multivariate analyses revealed a relationship between the differential gene expressions in liver and liver trioleate content and between blood glucose levels and a combination of differentially expressed genes measured in liver, IAT, and muscle. In summary, we have integrated gene expression and targeted metabolomic data to present a comprehensive overview of RSG-induced changes in a diabetes mouse model and improved the molecular understanding of how RSG ameliorates diabetes through its effect on the major insulin-sensitive tissues.