Regulation of adipocyte precursor DNA synthesis by acidic and basic fibroblast growth factors: interaction with heparin and other growth factors

Abstract

The development of adipose tissue is dependent on the growth and differentiation of fibroblast-like adipocyte precursor cells. Culture of adipocyte precursor cells in vitro has provided an ideal system for identifying potential regulators of proliferation and differentiation. We have demonstrated that both acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) stimulate chicken adipocyte precursor DNA synthesis in a dose-dependent manner up to a concentration of 100 micrograms aFGF/l and 1 microgram bFGF/l. The effect of bFGF was biphasic, so that in incubations with 25 micrograms bFGF/l, DNA synthesis was not significantly different from controls. In the presence of heparin, stimulation of DNA synthesis at 25 micrograms bFGF/l was 1.6-fold greater than at a concentration of 1 microgram bFGF/l. Addition of heparin to incubations containing aFGF reduced the concentration required for maximum stimulation of DNA synthesis to 1 microgram/l. Cells incubated with aFGF (1-100 micrograms/l) in combination with insulin-like growth factor-I (IGF-I), platelet-derived growth factor, transforming growth factor-alpha or transforming growth factor-beta 1 (TGF-beta 1) exhibited a marked synergistic increase in DNA synthesis. This was also the case when 1 microgram bFGF/l was used, but at a concentration of 25 micrograms bFGF/l synergy was only seen with IGF-I and TGF-beta 1. These results suggest that both basic and acidic FGF are potentially important regulators of adipocyte hyperplasia and that their effect is modulated by constituents of the extracellular matrix and the presence of other growth factors.