ABSTRACT

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.

Journal of Endocrinology (1991) 131, 203–209

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 μg aFGF/l and 1 μg bFGF/l. The effect of bFGF was biphasic, so that in incubations with 25 μg bFGF/l, DNA synthesis was not significantly different from controls. In the presence of heparin, stimulation of DNA synthesis at 25 μg bFGF/l was 1·6-fold greater than at a concentration of 1 μg bFGF/l. Addition of heparin to incubations containing aFGF reduced the concentration required for maximum stimulation of DNA synthesis to 1 μg/l. Cells incubated with aFGF (1–100 μg/l) in combination with insulin-like growth factor-I (IGF-I), platelet-derived growth factor, transforming growth factor-α or transforming growth factor-β1 (TGF-β1) exhibited a marked synergistic increase in DNA synthesis. This was also the case when 1 μg bFGF/l was used, but at a concentration of 25 pg bFGF/l synergy was only seen with IGF-I and TGF-β1. 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.

Journal of Endocrinology (1993) 137, 369–374

ABSTRACT

The hyperplastic capacity of adipose tissue resides in a group of fibroblast-like adipocyte precursor cells. There is evidence to suggest that their proliferation and differentiation is regulated by insulin-like growth factor-I (IGF-I) and transforming growth factor-β (TGF-β) but there is less information about other growth factors which may also participate in adipocyte precursor cell hyperplasia.

Transforming growth factor-α (TGF-α) is a 50 amino acid polypeptide which has been shown to stimulate proliferation in both neoplastic and normal cell types acting through the epidermal growth factor (EGF) receptor. We have studied the regulation of DNA synthesis and the activity of lipoprotein lipase by TGF-α in chicken adipocyte precursor cells in vitro. Both TGF-α and EGF stimulated incorporation of [³H]thymidine into DNA in a dose-dependent manner. TGF-α was approximately 180-fold more potent than EGF. Addition of TGF-α in combination with IGF-I, TGF-β1 or platelet-derived growth factor produced a synergistic increase in DNA synthesis. Short-term incubation with TGF-α reduced lipoprotein lipase activity by 23%.

These results show that TGF-α is a potent mitogen in these adipocyte precursor cells and can inhibit their differentiation in vitro and may participate in the regulation of adipose tissue development in vivo.

Journal of Endocrinology (1992) 134, 163–168