TY - JOUR
T1 - Effect of troglitazone on tumor necrosis factor α and transforming growth factor β expression and action in human adipocyte precursor cells in primary culture
AU - Skurk, Thomas
AU - Birgel, Michael
AU - Lee, Yu Mi
AU - Hauner, Hans
N1 - Funding Information:
This study was supported by a grant from the Hochschulsonderprogramm of the Government of Nordrhein-Westfalen. The financial support by Sankyo Europe GmbH, Düsseldorf, Germany, is gratefully acknowledged.
PY - 2006/3
Y1 - 2006/3
N2 - Troglitazone is a member of the class of thiazolidinediones that are known to act as insulin-sensitizing agents. Administration of these compounds ameliorates insulin resistance in type 2 diabetic patients, but may also promote weight gain. The main site of action is adipose tissue, where troglitazone binds to and activates the nuclear receptor peroxisome proliferator-activated receptor γ2. The aim of this study was to investigate whether troglitazone is able to affect the adipose expression and function of tumor necrosis factor α (TNF-α) and transforming growth factor β (TGF-β). Both TNF-α and TGF-β blocked adipose differentiation in vitro and led to a marked reduction in glycerol-3-phosphate dehydrogenase activity, a marker enzyme of adipose differentiation, by 69% ± 11% and 75% ± 15%, respectively. Addition of 2 μmol/L troglitazone significantly reduced this inhibitory effect of both cytokines on glycerol-3-phosphate dehydrogenase activity. Peroxisome proliferator-activated receptor γ messenger RNA (mRNA) was reduced by TNF-α in freshly isolated adipocytes. This effect was completely counteracted by troglitazone, whereas TGF-β had no immediate effect on peroxisome proliferator-activated receptor γ mRNA. Moreover, troglitazone alone promoted adipose differentiation in a time- and dose-dependent manner. Troglitazone treatment was found to result in a marked reduction of TNF-α mRNA expression in human preadipocytes to 54% ± 13% compared with untreated cultures. Furthermore, troglitazone was observed to partially antagonize the inhibitory effect of TNF-α on insulin-stimulated 2-deoxy-glucose uptake in newly differentiated human fat cells. In conclusion, troglitazone exerts a potent adipogenic activity in human preadipocytes, which may be mediated by suppression of the endogenous production of TNF-α and by counteracting the antiadipogenic effect of TGF-β. In addition, troglitazone improved insulin-stimulated glucose uptake in differentiated fat cells.
AB - Troglitazone is a member of the class of thiazolidinediones that are known to act as insulin-sensitizing agents. Administration of these compounds ameliorates insulin resistance in type 2 diabetic patients, but may also promote weight gain. The main site of action is adipose tissue, where troglitazone binds to and activates the nuclear receptor peroxisome proliferator-activated receptor γ2. The aim of this study was to investigate whether troglitazone is able to affect the adipose expression and function of tumor necrosis factor α (TNF-α) and transforming growth factor β (TGF-β). Both TNF-α and TGF-β blocked adipose differentiation in vitro and led to a marked reduction in glycerol-3-phosphate dehydrogenase activity, a marker enzyme of adipose differentiation, by 69% ± 11% and 75% ± 15%, respectively. Addition of 2 μmol/L troglitazone significantly reduced this inhibitory effect of both cytokines on glycerol-3-phosphate dehydrogenase activity. Peroxisome proliferator-activated receptor γ messenger RNA (mRNA) was reduced by TNF-α in freshly isolated adipocytes. This effect was completely counteracted by troglitazone, whereas TGF-β had no immediate effect on peroxisome proliferator-activated receptor γ mRNA. Moreover, troglitazone alone promoted adipose differentiation in a time- and dose-dependent manner. Troglitazone treatment was found to result in a marked reduction of TNF-α mRNA expression in human preadipocytes to 54% ± 13% compared with untreated cultures. Furthermore, troglitazone was observed to partially antagonize the inhibitory effect of TNF-α on insulin-stimulated 2-deoxy-glucose uptake in newly differentiated human fat cells. In conclusion, troglitazone exerts a potent adipogenic activity in human preadipocytes, which may be mediated by suppression of the endogenous production of TNF-α and by counteracting the antiadipogenic effect of TGF-β. In addition, troglitazone improved insulin-stimulated glucose uptake in differentiated fat cells.
UR - http://www.scopus.com/inward/record.url?scp=32544448031&partnerID=8YFLogxK
U2 - 10.1016/j.metabol.2005.09.004
DO - 10.1016/j.metabol.2005.09.004
M3 - Article
C2 - 16483873
AN - SCOPUS:32544448031
SN - 0026-0495
VL - 55
SP - 309
EP - 316
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 3
ER -
