Adipose tissue growth can occur by both hypertrophy and hyperplasia. The capacity for adipocyte hyperplasia in vivo resides in a population of fibroblast-like adipocyte precursor cells but the regulation of the proliferation of these cells by growth factors has not been well characterized. This study was designed to determine the effects of the insulin-like growth factors (IGF-I and IGF-II), platelet-derived growth factor (PDGF) and transforming growth factor-β1 (TGF-β1) added alone or together on the proliferation of primary adipocyte precursor cells in vitro. Adipocyte precursor cell proliferation measured by [3H]thymidine incorporation into DNA was stimulated by all of these growth factors and was particularly marked with PDGF. IGF-I or IGF-II added together with TGF-β1 produced a greater than additive response and the effect of PDGF was synergistic with that of IGF-I at certain concentrations.
Stimulation of proliferation of some cell types by TGF-β has been linked to the secondary production of PDGF but the evidence we have suggests that this is unlikely in chicken adipocyte precursors. DNA synthesis in response to TGF-β1 required only a short exposure to the peptide, and conditioned medium from chicken adipocyte precursor cells previously exposed to TGF-β had no effect on DNA synthesis when added to fresh batches of cells. Addition of TGF-β1 together with PDGF produced a synergistic effect whereas an additive effect would be expected if PDGF mediated the effect of TGF-β1.
IGF-I mRNA is expressed in the Ob 1771 preadipocyte cell line during differentiation, in stromalvascular cells from adipose tissue, and TGF-β mRNA is expressed in both proliferating and differentiating 3T3-L1 preadipocytes. Together with the data presented here, this would indicate that these peptides have a role in adipocyte development by an autocrine or paracrine mechanism although the source of PDGF in vivo is at present unknown.