Effect of transforming growth factor-beta on insulin-like growth factor 1- and dexamethasone-induced proliferation and differentiation in primary cultures of pig preadipocytes.

The purpose of this study was to examine the effects of a known inhibitor, transforming growth factor-beta1 (TGF-beta1) versus the known stimulators insulin-like growth factor-1 (IGF-1) and dexamethasone (DEX) on pig preadipocyte differentiation in serum and serum-free primary cultures. In cultures with serum, preadipocyte and nonpreadipocyte replication was increased (p < 0.02) by IGF-1 and by TGF-beta1 (p < 0.05; p < 0.001). IGF-1 (10 nM) enhanced preadipocyte differentiation (p < 0.05) in serum-supplemented (1% pig serum) cultures, whereas TGF-beta1 (15 pM) reduced preadipocyte differentiation (p < 0.01) in the presence and absence of IGF-1. Furthermore, GPDH (SN-glycerol-3-phosphate dehydrogenase) specific activity (marker that indicates differentiation) was decreased (p < 0.05) by adding TGF-beta1 to serum-free cultures, but TGF-beta1 had little effect in serum-supplemented cultures. DEX significantly enhanced GPDH activity and fat cell cluster number, whereas pretreatment with TGF-beta1 eliminated the DEX enhancement. We have shown for the first time that TGF-beta can decrease (p < 0.01) the cellular secretion of IGF-1 by pig adipose tissue cells and counter the effects of exogenous IGF-1. These studies indicate that TGF-beta1 may not inhibit adipocyte development in the initial growth phase, but may inhibit differentiation and/or hypertrophy (lipid filling) at a later stage of development.