Fibroblast growth factor receptor 1 is a key regulator of early adipogenic events in human preadipocytes

Widberg, C. H., Newell, F. S., Bachmann, A. W., Ramnoruth, S. N., Spelta, M. C., Whitehead, J. P., Hutley, L. J. and Prins, J. B. (2009) Fibroblast growth factor receptor 1 is a key regulator of early adipogenic events in human preadipocytes. American Journal of Physiology Endocrinology and Metabolism, 296 1: E121-E131. doi:10.1152/ajpendo.90602.2008


Author Widberg, C. H.
Newell, F. S.
Bachmann, A. W.
Ramnoruth, S. N.
Spelta, M. C.
Whitehead, J. P.
Hutley, L. J.
Prins, J. B.
Title Fibroblast growth factor receptor 1 is a key regulator of early adipogenic events in human preadipocytes
Journal name American Journal of Physiology Endocrinology and Metabolism   Check publisher's open access policy
ISSN 0193-1849
1522-1555
Publication date 2009-01-01
Year available 2008
Sub-type Article (original research)
DOI 10.1152/ajpendo.90602.2008
Open Access Status DOI
Volume 296
Issue 1
Start page E121
End page E131
Total pages 11
Place of publication Bethesda, MD, United States
Publisher American Physiological Society
Language eng
Subject C1
920106 Endocrine Organs and Diseases (excl. Diabetes)
110306 Endocrinology
1116 Medical Physiology
Abstract 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, platelet-derived growth factor (PDGF; AA and BB) and vascular endothelial growth factor. Although 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 FGF receptor (FGFR) tyrosine kinase activity, using the FGFR-specific inhibitors PD-173074 and SU-5402, revealed an obligate requirement for FGFR activity in these processes. A combination of biochemical and genetic approaches revealed an important role for FGFR1. Knock down of FGFR1 expression by small-interfering RNA reduced FGF-1-stimulated signaling events, proliferation, and priming. Together these data highlight the unique nature of the role of FGF-1 during the earliest stages of adipogenesis and establish a role for FGFR1 in human adipogenesis, identifying FGFR1 as a potential therapeutic target to reduce obesity.
Keyword Preadipocyte
Obesity
Adipogenesis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes First published October 21, 2008

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
UQ Diamantina Institute Publications
 
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Created: Tue, 31 Mar 2009, 23:45:48 EST by Kylie Hengst on behalf of UQ Diamantina Institute