Dexamethasone reverses TGF-β-mediated inhibition of primary rat preadipocyte differentiation

Abstract

Dexamethasone and transforming growth factor-β (TGF-β) show contrary effects on differentiation of adipocytes. Dexamethasone stimulates adipocyte differentiation whereas TGF-β inhibits it. In the present study, we investigated whether dexamethasone could reverse the TGF-β-mediated inhibition of preadipocyte differentiation. Primary rat preadipocytes, obtained from Sprague-Dawley rats, were pretreated with dexamethasone in the presence or absence of TGF-β, prior to the induction of differentiation. Co-treatment of dexamethasone and TGF-β before inducing differentiation reversed the TGF-β-mediated inhibition of preadipocyte differentiation. In order to elucidate the mechanism by which dexamethasone reversed the effect of TGF-β on the inhibition of preadipocyte differentiation, the expression of CCAAT/enhancer binding protein-α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) was examined. Dexamethasone increased C/EBPα and PPARγ expression in the absence of TGF-β and also recovered the TGF-β-mediated suppression of C/EBPα expression in preadipocytes. Its effect was sustained in differentiated adipocytes as well. However, those effects were not observed in 3T3-L1 preadipocytes or differentiated adipocytes. These results indicate that dexamethasone reverses the TGF-β-mediated suppression of adipocyte differentiation by regulating the expression of C/EBPα and PPARγ, which is dependent on the cellular context.