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

• Published in: The journal of clinical endocrinology and metabolism Vol. 92; no. 2; pp. 720 - 724
• Main Authors: Kolak, Maria, Yki-Järvinen, Hannele, Kannisto, Katja, Tiikkainen, Mirja, Hamsten, Anders, Eriksson, Per, Fisher, Rachel M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.02.2007
• Subjects: Adipose Tissue - drug effects; Adipose Tissue - physiology; Biological and medical sciences; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Gene Expression Profiling; Humans; Hypoglycemic Agents - administration & dosage; Male; Medical sciences; Medicin och hälsovetenskap; Metformin - administration & dosage; Middle Aged; Thiazolidinediones - administration & dosage; Vertebrates: endocrinology; Endocrinopathy; Type 2 diabetes; Human; Adipose tissue; Metabolic diseases; Thiazolidinedione derivatives; Gene expression; In vivo; Chronic; Treatment; Rosiglitazone; Gene therapy; Endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2006-1465

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. α-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)], 11β-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.