Fibroblast growth factors (FGFs) are important intercellular signaling molecules in developmental processes.Here, we show that FGF10 is secreted by cultured preadipocytes and that prevention of FGF10 signaling inhibits the expression of C/EBP and the subsequent differentiation of these cells. An active form of C/EBP rescued differentiation of the cells in which FGF10 signaling was blocked. Development of white adipose tissue and the expression of C/EBP in this tissue of FGF10 knockout mice were markedly reduced, and the ability of embryonic fibroblasts derived from FGF10 knockout mice to differentiate into adipocytes was impaired. Therefore, FGF10 plays an important role in adipogenesis, at least partly by contributing to the expression of C/EBP through an autocrine/paracrine mechanism. Received February 8, 2002; revised version accepted March 1, 2002. Adipose tissue contributes to regulation of energy balance, not only by serving as a reservoir of triglycerides but also by secreting circulating factors that affect food intake or metabolism (Hwang et al. 1997;Rosen and Spiegelman 2000;Fruebis et al. 2001;Steppan et al. 2001). Mature adipocytes do not undergo cell division; the number of these cells is therefore thought to increase as a result of the proliferation of preadipocytes and their subsequent differentiation into mature adipocytes. Various factors secreted by adipocytes or preadipocytes have been identified (Hwang et al. 1997;Rosen and Spiegelman 2000;MacDougald and Mandrup 2002), some of which, such as tumor necrosis factor-␣ (Petrunschke and Hauner 1994), Pref-1 (Smas et al. 1997), and Wnt-10b (Ross et al. 2000), regulate adipogenesis by inhibiting the differentiation of these cells. Although factors that promote the proliferation or differentiation of preadipocytes have also been shown to be secreted by such cells isolated from obese humans (Lau et al. 1987) or by mature rat adipocytes (Schillabeer et al. 1989), the nature of these factors has remained unclear.The fibroblast growth factor (FGF) family comprises at least 23 proteins (Yamashita et al. 2000;Ornitz and Itoh 2001) that function in an autocrine or paracrine manner and play important roles in the development, maintenance, and repair of tissues (Goldfarb 1996;Ornitz and Itoh 2001). FGF10 was initially identified in rat embryos by homology-based polymerase chain reaction (PCR; Yamasaki et al. 1996). Disruption of the FGF10 gene resulted in complete absence of limb bud formation and severe defects in the branching morphogenesis of the lung (Min et al. 1998;Sekine et al. 1999), indicating that FGF10 is important for development of these organs. On the other hand, we have previously shown that, among the major adult tissues, transcripts of the FGF10 gene are most abundant in adipose tissue . Brown adipose tissue (BAT) and white adipose tissue (WAT) constitute the two principal types of adipose tissue and perform distinct functions (Hwang et al. 1997;Rosen and Spiegelman 2000). The expression of FGF10 is restricted to WAT. In particular, F...