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Submitted on July 7, 2006
Accepted on November 22, 2006
Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden. Department of Medicine, Division of Diabetes, University of Helsinki, PO Box 340, 00029 Helsinki, Finland. Minerva Institute for Medical Research, Minerva, Helsinki, Finland
* To whom correspondence should be addressed. E-mail: rachel.fisher{at}ki.se.
Objective: 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, 7 men) were randomized to receive either rosiglitazone (n = 9, 8 mg/day) or metformin (n = 11, 2 g/day) for 16 weeks. Sc adipose tissue biopsies were taken before and after treatment. Expression of 50 genes, previously shown to be altered by thiazolidinediones (TZDs) 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. stearoyl-CoA desaturase (3.2-fold), CD36 (1.8-fold)), structural genes (e.g. alpha-1 type-1 procollagen (1.7-fold)) and GLUT4 (1.5-fold), and decreased expression of inflammation-related genes (e.g. interleukin 6 (0.6-fold), chemokine (C-C motif) ligand 3 (0.4-fold)), 11
-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 TZD action in human adipose tissue and experimental models.
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