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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.

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