PROLIFERATION AND DIFFERENTIATION OF RAT ADIPOSE PRECURSOR CELLS IN CHEMICALLY-DEFINED MEDIUM - DIFFERENTIAL ACTION OF ANTI-ADIPOGENIC AGENTS

Primary rat adipose precursor cells, maintained in the minimal chemically defined medium (ITT medium) able to promote differentiation, have been used to investigate the ability of several agents to modulate their proliferation and their differentiation. Fetuin and fibroblast growth factor (FGF), which exhibited a strong and a weak mitogenic activity, respectively, do not significantly affect the proportion of differentiated cells as indicated by glycerol-3-phosphate dehydrogenase (GPDH) activity values. In contrast, carbaprostacyclin (cPGl(2)), a stable analogue of prostacyclin, behaves as a true adipogenic factor leading to a 4 to 5-fold increase in GPDH-specific activities with no significant effect on cell growth. Submaxillary gland kallikrein (SMGK), transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) behave as growth-promoting agents but at the same time elicit a dose-dependent inhibition of differentiation. Epidermal growth factor (EGF) and prostaglandin F-2 alpha (PGF(2 alpha)) do not show any effect on cell proliferation at concentrations which exert a maximal inhibitory action on differentiation. Upon removal of EGF from the culture medium, complete resumption of differentiation occurs, whereas upon removal of PGF(2 alpha) or SMGK, complete resumption only takes place when differentiation is triggered by cPGl(2). Upon removal of TNF-alpha, a partial resumption of differentiation is observed, whereas no subsequent differentiation is observed upon TCF-beta removal. These results emphasize the adipogenic, nonmitogenic role of cPGl(2) and also allow the distinction between the various adipogenic/mitogenic factors which affect adipose cell differentiation. (C) 1994 Wiley-Liss, Inc.