This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Patel, N. G. Articles by Eggo, M. C. Search for Related Content PubMed PubMed Citation Articles by Patel, N. G. Articles by Eggo, M. C. Related Collections Lipid Obesity

Essential Role of Fibroblast Growth Factor Signaling in Preadipoctye Differentiation

Division of Medical Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom

Address all correspondence and requests for reprints to: Dr. Margaret C. Eggo, Division of Medical Sciences, The Medical School, University of Birmingham, Birmingham B15 2TT, United Kingdom. E-mail: M.C.Eggo{at}bham.ac.uk.

We have examined the expression and role of autocrine fibroblast growth factors (FGFs) in human preadipocytes through their differentiation in vitro. A high-molecular weight form of FGF-2 was initially strongly expressed, but 6–9 d after induction of differentiation, its expression decreased markedly. This coincided with the first appearance of visible lipid droplets within the cells. FGF-2 (18 kDa) was not found. FGF receptor (FGFR) 1 was detected as a single band of 125 kDa that also decreased with differentiation. Its decrease preceded that of FGF-2. Despite the decrease in cell-associated FGF-2 with differentiation, secreted FGF-2 was 2.5-fold higher in the differentiated preadipocytes. To determine whether FGF-2 had an autocrine role, FGFR signaling was inhibited using recombinant adenovirus expressing dominant negative FGFR1 (RAdDN-FGFR1) and a specific inhibitor of FGFR1 signaling, PD166866. Preadipocytes transduced with RAdDN-FGFR1 expressed a truncated, 79-kDa FGFR1. Differentiation, assessed by lipid droplet formation, was completely prevented by RAdDN-FGFR1 and by PD166866. The protein content in the cell layer and glucose uptake were significantly reduced by both agents. The insulin-sensitizing drug, rosiglitazone, did not prevent the actions of RAdDN-FGFR1 or PD166866. Controlling adipose tissue growth by limiting FGF actions may provide a means to combat obesity.

This article has been cited by other articles:

				T. Shimada, N. Hiramatsu, K. Hayakawa, S. Takahashi, A. Kasai, Y. Tagawa, M. Mukai, J. Yao, Y. Fujii-Kuriyama, and M. Kitamura Dual suppression of adipogenesis by cigarette smoke through activation of the aryl hydrocarbon receptor and induction of endoplasmic reticulum stress Am J Physiol Endocrinol Metab, April 1, 2009; 296(4): E721 - E730. [Abstract] [Full Text] [PDF]

				C. H. Widberg, F. S. Newell, A. W. Bachmann, S. N. Ramnoruth, M. C. Spelta, J. P. Whitehead, L. J. Hutley, and J. B. Prins Fibroblast growth factor receptor 1 is a key regulator of early adipogenic events in human preadipocytes Am J Physiol Endocrinol Metab, January 1, 2009; 296(1): E121 - E131. [Abstract] [Full Text] [PDF]

				H. D. Sun, M. Malabunga, J. R. Tonra, R. DiRenzo, F. E. Carrick, H. Zheng, H.-R. Berthoud, O. P. McGuinness, J. Shen, P. Bohlen, et al. Monoclonal antibody antagonists of hypothalamic FGFR1 cause potent but reversible hypophagia and weight loss in rodents and monkeys Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E964 - E976. [Abstract] [Full Text] [PDF]

				V. W.M. van Hinsbergh and T. J. Rabelink FGFR1 and the Bloodline of the Vasculature Arterioscler Thromb Vasc Biol, May 1, 2005; 25(5): 883 - 886. [Full Text] [PDF]