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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.

Authors :
Le Bouter S
Rodriguez M
Guigal-Stephan N
Courtade-Gaïani S
Xuereb L
de Montrion C
Croixmarie V
Umbdenstock T
Boursier-Neyret C
Lonchampt M
Brun M
Dacquet C
Ktorza A
Lockhart BP
Galizzi JP
Source :
PPAR research [PPAR Res] 2010; Vol. 2010. Date of Electronic Publication: 2010 Oct 10.
Publication Year :
2010

Abstract

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.

Details

Language :
English
ISSN :
1687-4765
Volume :
2010
Database :
MEDLINE
Journal :
PPAR research
Publication Type :
Academic Journal
Accession number :
20953342
Full Text :
https://doi.org/10.1155/2010/679184