This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted 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 Kolak, M. Articles by Fisher, R. M. Search for Related Content PubMed PubMed Citation Articles by Kolak, M. Articles by Fisher, R. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Diabetes Hazardous Substances DB METFORMIN HYDROCHLORIDE Related Collections Diabetes and Insulin Metabolism

Effects of Chronic Rosiglitazone Therapy on Gene Expression in Human Adipose Tissue in Vivo in Patients with Type 2 Diabetes

Atherosclerosis Research Unit (M.K., K.K., A.H., P.E., R.M.F.), King Gustaf V Research Institute, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden; Department of Medicine (H.Y.-J., M.T.), Division of Diabetes, University of Helsinki, 00029 Helsinki, Finland; and Minerva Institute for Medical Research (H.Y.-J.), 00290 Helsinki, Finland

Address all correspondence and requests for reprints to: Rachel M. Fisher, Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Karolinska University Hospital M1:01, 171 76 Stockholm, Sweden. E-mail: rachel.fisher{at}ki.se.

Objective: The aim of this study was to compare effects of therapeutic doses of rosiglitazone and metformin on expression of 50 genes in human adipose tissue in vivo.

Methods: Twenty patients with diet-treated type 2 diabetes (13 women, seven men) were randomized to receive either rosiglitazone (n = 9; 8 mg/d) or metformin (n = 11; 2 g/d) for 16 wk. Subcutaneous adipose tissue biopsies were performed before and after treatment. Expression of 50 genes, previously shown to be altered by thiazolidinediones in experimental models, was quantified by real-time PCR and normalized to two housekeeping genes.

Results: Rosiglitazone, but not metformin, treatment increased expression of genes involved in triacylglycerol storage [e.g. stearyl-CoA desaturase (3.2-fold), CD36 (1.8-fold)], structural genes [e.g. -1 type-1 procollagen (1.7-fold) and GLUT4 (1.5-fold)], and decreased expression of inflammation-related genes [e.g. IL-6 (0.6-fold), chemokine (C-C motif) ligand 3 (0.4-fold)], 11ß-hydroxysteroid dehydrogenase 1 (0.6-fold), and resistin (0.3-fold) (all P < 0.05).

Conclusions: These results suggest that the insulin-sensitizing action of rosiglitazone involves remodeling of human adipose tissue to reduce inflammation and promote lipid storage. Furthermore, we show some important differences between thiazolidinedione action in human adipose tissue and experimental models.

This article has been cited by other articles:

				D.-E. Lee, S. Kehlenbrink, H. Lee, M. Hawkins, and J. S. Yudkin Getting the message across: mechanisms of physiological cross talk by adipose tissue Am J Physiol Endocrinol Metab, June 1, 2009; 296(6): E1210 - E1229. [Abstract] [Full Text] [PDF]

				P. A. Permana, W. Zhang, M. Wabitsch, P. Fischer-Posovszky, W. C. Duckworth, and P. D. Reaven Pioglitazone reduces inflammatory responses of human adipocytes to factors secreted by monocytes/macrophages Am J Physiol Endocrinol Metab, May 1, 2009; 296(5): E1076 - E1084. [Abstract] [Full Text] [PDF]

				A. Yao-Borengasser, N. Rassouli, V. Varma, A. M. Bodles, N. Rasouli, R. Unal, B. Phanavanh, G. Ranganathan, R. E. McGehee Jr., and P. A. Kern Stearoyl-Coenzyme A Desaturase 1 Gene Expression Increases after Pioglitazone Treatment and Is Associated with Peroxisomal Proliferator-Activated Receptor-{gamma} Responsiveness J. Clin. Endocrinol. Metab., November 1, 2008; 93(11): 4431 - 4439. [Abstract] [Full Text] [PDF]

				A. Oberbach, S. Lehmann, K. Kirsch, J. Krist, M. Sonnabend, A. Linke, A. Tonjes, M. Stumvoll, M. Bluher, and P. Kovacs Long-term exercise training decreases interleukin-6 (IL-6) serum levels in subjects with impaired glucose tolerance: effect of the -174G/C variant in IL-6 gene Eur. J. Endocrinol., August 1, 2008; 159(2): 129 - 136. [Abstract] [Full Text] [PDF]

				G. J. Hausman, S. P. Poulos, T. D. Pringle, and M. J. Azain The influence of thiazolidinediones on adipogenesis in vitro and in vivo: Potential modifiers of intramuscular adipose tissue deposition in meat animals J Anim Sci, April 1, 2008; 86(14_suppl): E236 - E243. [Abstract] [Full Text] [PDF]