Role of Fgf10 in cell proliferation in white adipose tissue

The development of white adipose tissue (WAT) involves adipogenesis and cell proliferation. Although the adipogenesis has been well studied, the cell proliferation has not. Therefore, we examined the mechanism of the proliferation by analyzing Fgf10(-/-) mouse embryonic WAT, in which adipogenesis and proliferation were severely impaired. D-type cyclin expression and retinoblastoma family protein phosphorylation essential for cell proliferation were examined in WAT. Both cyclin D2 expression and p130 phosphorylation were impaired in the Fgf10(-/-) WAT. In mouse embryonic fibroblasts, Fgf10 stimulated cyclin D2 expression and p130 phosphorylation, which were inhibited by an inhibitor of the Ras/MAPK pathway. These results suggest that Fgf10 stimulates cell proliferation in WAT through the Ras/MAPK pathway followed by the cyclin D2-dependent phosphorylation of p130. In contrast, expression but not phosphorylation of pRb was impaired in the Fgf10(-/-) WAT. As pRb is essential for adipogenesis, Fgf10 might play a role in adipogenesis by inducing its expression.