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Essential role of fibroblast growth factor signaling in preadipoctye differentiation
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Patel, Nayan G., Kumar, Sudhesh and Eggo, Margaret C. (2005) Essential role of fibroblast growth factor signaling in preadipoctye differentiation. The Journal of Clinical Endocrinology & Metabolism, Volume 90 (Number 2). pp. 1226-1232. doi:10.1210/jc.2004-1309
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Official URL: http://dx.doi.org/10.1210/jc.2004-1309
Abstract
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.
| Item Type: | Journal Article | ||||
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | The Journal of Clinical Endocrinology & Metabolism | ||||
| Publisher: | The Endocrine Society | ||||
| ISSN: | 0021-972X | ||||
| Official Date: | 2005 | ||||
| Dates: |
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| Volume: | Volume 90 | ||||
| Number: | Number 2 | ||||
| Page Range: | pp. 1226-1232 | ||||
| DOI: | 10.1210/jc.2004-1309 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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