Requirement of fibroblast growth factor 10 in development of white adipose tissue

Abstract

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...

FGFR2IIIb signaling regulates thymic epithelial differentiation

“…1g-i), indicating that these cells were acquiring features of adipocytes. This finding may reflect the reported ability of FGF10 to act as a growth factor for preadipocytes (Sakaue et al, 2002) and is likely related to the expansion of the thymic mesenchymal compartment (described below). Concomitant with these stromal alterations, elevated FGFR2IIIb signaling also had a profound effect on the vascular organization of the thymus.…”

Functional evolutionary history of the mouse Fgf gene family

“…Fgf9, Fgf10, and Fgf18 knockout mice died shortly after birth. Fgf10 is critical for epithelial-mesenchymal interactions necessary for the development of epithelial components of multiple organs (Min et al, 1998;Sekine et al, 1999;Ohuchi et al, 2000;Sakaue et al, 2002). Fgf9 and Fgf18 have essential roles in the development of mesenchymal components of multiple organs (Colvin et al, 2001a, 2001b, Ohbayashi et al, 2002Liu et al, 2002;Usui et al, 2004).…”

Skp2 Controls Adipocyte Proliferation during the Development of Obesity

“…Immunoblot and Quantitative Reverse Transcription-PCR Analyses-Immunoblot analysis was performed as described previously (30,31). Reverse transcription and real-time PCR analysis was also performed as described (32) with a Sequence detector (model 7900, Applied Biosystems) and with 36B4 mRNA as the invariant control.…”