Submitted on July 16, 2008
Revised on September 30, 2008
Accepted on October 20, 2008
Fibroblast Growth Factor Receptor 1 is a Key Regulator of Early Adipogenic Events in Human Preadipocytes
Charlotte H Widberg1, Felicity S Newell1, Anthony W Bachmann1, Sakoontalla N Ramnoruth1, Madonna C Spelta1, Jonathan P Whitehead1, Louise J Hutley1, and Johannes Bernhard Prins2*
1 University of Queensland
2 Diamantina Institute for Cancer Immunology and Metabolic Medicine, University of Queensland
* To whom correspondence should be addressed. E-mail: j.prins{at}uq.edu.au.
Cell number is an important determinant of adipose tissue mass and the coordinated proliferation and differentiation of preadipocytes into mature lipid laden adipocytes underpins the increased adipose tissue mass associated with obesity. Despite this the molecular cues governing such adipose tissue expansion are poorly understood. We previously reported that Fibroblast Growth Factor-1 (FGF-1) promotes both proliferation and differentiation of human preadipocytes and that the major adipogenic effect of FGF-1 occurs during proliferation, priming the cells for adipose conversion. In the current study we examined whether this effect was linked to the mitogenic action of FGF-1 by investigating the mitogenic and adipogenic potential of other growth factors, PDGF (AA and BB) and VEGF. While PDGF-AA and PDGF-BB showed comparable mitogenic potential to FGF-1, only FGF-1 treatment resulted in priming and subsequent differentiation. Pharmacological inhibition of FGFR tyrosine kinase activity, using the FGFR-specific inhibitors PD173074 and SU5402, revealed an obligate requirement for FGFR activity in these processes. A combination of biochemical and genetic approaches revealed an important role for FGFR1. Knockdown of FGFR1 expression by siRNA reduced FGF-1-stimulated signaling events, proliferation and priming. Together these data highlight the unique nature of the role of FGF-1during the earliest stages of adipogenesis and establish a role for FGFR1 in human adipogenesis, identifying FGFR1 as a potential therapeutic target to reduce obesity.
