Effects of chronic rosiglitazone therapy on gene expression in human adipose tissue in vivo in patients with type 2 diabetes.
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. alpha-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)], 11beta-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.
Kolak
Maria
M
Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Karolinska University Hospital M1:01, 171 76 Stockholm, Sweden.
Yki-Järvinen
Hannele
H
Kannisto
Katja
K
Tiikkainen
Mirja
M
Hamsten
Anders
A
Eriksson
Per
P
Fisher
Rachel M
RM
D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000008:administration & dosage; D008875:Middle Aged; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin