Article: Fibroblast growth factor 21 induces glucose transporter-1 expression through activation of the serum response factor/Ets-like protein-1 in adipocytes
| Title | Fibroblast growth factor 21 induces glucose transporter-1 expression through activation of the serum response factor/Ets-like protein-1 in adipocytes | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Ge, X1 Chen, C1 Hui, X1 Wang, Y1 Lam, KSL1 Xu, A1 | ||||||
| Issue Date | 2011 | ||||||
| Publisher | American Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/ | ||||||
| Citation | Journal Of Biological Chemistry, 2011, v. 286 n. 40, p. 34533-34541 [How to Cite?] DOI: http://dx.doi.org/10.1074/jbc.M111.248591 | ||||||
| Abstract | Fibroblast growth factor 21 (FGF21) is a liver-secreted endocrine factor with multiple beneficial effects on obesity-related disorders. It enhances glucose uptake by inducing the expression of glucose transporter-1 (GLUT1) in adipocytes. Here we investigated the signaling pathways that mediate FGF21-induced GLUT1 expression and glucose uptake in vitro and in animals. Quantitative real-time PCR and a luciferase reporter assay showed that FGF21 induced GLUT1 expression through transcriptional activation. The truncation of the GLUT1 promoter from -3145 to -3105 bp, which contains two highly conserved serum response element (SRE) and E-Twenty Six (ETS) binding motif, dramatically decreased FGF21-induced promoter activity of the GLUT1 gene. A chromatin immunoprecipitation assay demonstrated that the transcription factors serum response factor (SRF) and Ets-like protein-1 (Elk-1) were recruited to the GLUT1 promoter upon FGF21 stimulation. The siRNA-mediated knockdown of either SRF or Elk-1 resulted in a marked attenuation in FGF21-induced GLUT1 expression and glucose uptake in adipocytes. In C57 lean mice, a single intravenous injection of FGF21 induced phosphorylation of Elk-1 at Ser 383 and SRF at Ser 103 and also led to the recruitment of Elk-1 and SRF to the GLUT1 promoter in epididymal fats. By contrast, such effects of in vivo FGF21 administration were blunted in high fat diet-induced obese mice. In conclusion, FGF21 induces GLUT1 expression and glucose uptake through sequential activation of ERK1/2 and SRF/Elk-1, which in turn triggers the transcriptional activation of GLUT1 in adipocytes. The impairment in this signaling pathway may contribute to FGF21 resistance in obese mice. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc. | ||||||
| ISSN | 0021-9258 2011 Impact Factor: 4.773 2011 SCImago Journal Rankings: 0.793 | ||||||
| DOI | http://dx.doi.org/10.1074/jbc.M111.248591 | ||||||
| ISI Accession Number ID | WOS:000295406300007
Funding Information: This work was supported by Collaborative Research Fund (HKU3/09C) from the Research Grant Council of Hong Kong, Seeding fund for basic research, and matching funding for national 973 projects from the University of Hong Kong (to A. X.). | ||||||
| PubMed Central ID | PMC3186365 | ||||||
| References | References in Scopus |
| dc.contributor.author | Ge, X | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Chen, C | ||||||
| dc.contributor.author | Hui, X | ||||||
| dc.contributor.author | Wang, Y | ||||||
| dc.contributor.author | Lam, KSL | ||||||
| dc.contributor.author | Xu, A | ||||||
| dc.date.accessioned | 2011-12-21T08:54:10Z | ||||||
| dc.date.available | 2011-12-21T08:54:10Z | ||||||
| dc.date.issued | 2011 | ||||||
| dc.description.abstract | Fibroblast growth factor 21 (FGF21) is a liver-secreted endocrine factor with multiple beneficial effects on obesity-related disorders. It enhances glucose uptake by inducing the expression of glucose transporter-1 (GLUT1) in adipocytes. Here we investigated the signaling pathways that mediate FGF21-induced GLUT1 expression and glucose uptake in vitro and in animals. Quantitative real-time PCR and a luciferase reporter assay showed that FGF21 induced GLUT1 expression through transcriptional activation. The truncation of the GLUT1 promoter from -3145 to -3105 bp, which contains two highly conserved serum response element (SRE) and E-Twenty Six (ETS) binding motif, dramatically decreased FGF21-induced promoter activity of the GLUT1 gene. A chromatin immunoprecipitation assay demonstrated that the transcription factors serum response factor (SRF) and Ets-like protein-1 (Elk-1) were recruited to the GLUT1 promoter upon FGF21 stimulation. The siRNA-mediated knockdown of either SRF or Elk-1 resulted in a marked attenuation in FGF21-induced GLUT1 expression and glucose uptake in adipocytes. In C57 lean mice, a single intravenous injection of FGF21 induced phosphorylation of Elk-1 at Ser 383 and SRF at Ser 103 and also led to the recruitment of Elk-1 and SRF to the GLUT1 promoter in epididymal fats. By contrast, such effects of in vivo FGF21 administration were blunted in high fat diet-induced obese mice. In conclusion, FGF21 induces GLUT1 expression and glucose uptake through sequential activation of ERK1/2 and SRF/Elk-1, which in turn triggers the transcriptional activation of GLUT1 in adipocytes. The impairment in this signaling pathway may contribute to FGF21 resistance in obese mice. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc. | ||||||
| dc.description.nature | link_to_OA_fulltext | ||||||
| dc.identifier.citation | Journal Of Biological Chemistry, 2011, v. 286 n. 40, p. 34533-34541 [How to Cite?] DOI: http://dx.doi.org/10.1074/jbc.M111.248591 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1074/jbc.M111.248591 | ||||||
| dc.identifier.epage | 34541 | ||||||
| dc.identifier.hkuros | 197855 | ||||||
| dc.identifier.isi | WOS:000295406300007
Funding Information: This work was supported by Collaborative Research Fund (HKU3/09C) from the Research Grant Council of Hong Kong, Seeding fund for basic research, and matching funding for national 973 projects from the University of Hong Kong (to A. X.). | ||||||
| dc.identifier.issn | 0021-9258 2011 Impact Factor: 4.773 2011 SCImago Journal Rankings: 0.793 | ||||||
| dc.identifier.issue | 40 | ||||||
| dc.identifier.pmcid | PMC3186365 | ||||||
| dc.identifier.pmid | 21846717 | ||||||
| dc.identifier.scopus | eid_2-s2.0-80053428117 | ||||||
| dc.identifier.spage | 34533 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/143765 | ||||||
| dc.identifier.volume | 286 | ||||||
| dc.language | eng | ||||||
| dc.publisher | American Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/ | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | Journal of Biological Chemistry | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | Journal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc. | ||||||
| dc.rights | This research was originally published in [Journal of Biological Chemistry]. Xuan Ge, Cheng Chen, Xiaoyan Hui, Yu Wang, Karen S. L. Lam, and Aimin Xu. Fibroblast Growth Factor 21 Induces Glucose Transporter-1 Expression through Activation of the Serum Response Factor/Ets-Like Protein-1 in Adipocytes. Journal of Biological Chemistry. 2011. Vol 286:pp34533-pp34541. © the American Society for Biochemistry and Molecular Biology | ||||||
| dc.subject.mesh | Adipocytes - metabolism | ||||||
| dc.subject.mesh | Fibroblast Growth Factors - metabolism | ||||||
| dc.subject.mesh | Glucose Transport Proteins, Facilitative - biosynthesis | ||||||
| dc.subject.mesh | Serum Response Factor - metabolism | ||||||
| dc.subject.mesh | ets-Domain Protein Elk-1 - biosynthesis | ||||||
| dc.title | Fibroblast growth factor 21 induces glucose transporter-1 expression through activation of the serum response factor/Ets-like protein-1 in adipocytes | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong