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Article: Fibroblast growth factor 21 induces glucose transporter-1 expression through activation of the serum response factor/Ets-like protein-1 in adipocytes
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TitleFibroblast growth factor 21 induces glucose transporter-1 expression through activation of the serum response factor/Ets-like protein-1 in adipocytes
 
AuthorsGe, X1
Chen, C1
Hui, X1
Wang, Y1
Lam, KSL1
Xu, A1
 
Issue Date2011
 
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
 
CitationJournal Of Biological Chemistry, 2011, v. 286 n. 40, p. 34533-34541 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M111.248591
 
AbstractFibroblast 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.
 
ISSN0021-9258
2012 Impact Factor: 4.651
2012 SCImago Journal Rankings: 2.723
 
DOIhttp://dx.doi.org/10.1074/jbc.M111.248591
 
PubMed Central IDPMC3186365
 
ISI Accession Number IDWOS:000295406300007
Funding AgencyGrant Number
Research Grant Council of Hong KongHKU3/09C
University of Hong Kong
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.).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorGe, X
 
dc.contributor.authorChen, C
 
dc.contributor.authorHui, X
 
dc.contributor.authorWang, Y
 
dc.contributor.authorLam, KSL
 
dc.contributor.authorXu, A
 
dc.date.accessioned2011-12-21T08:54:10Z
 
dc.date.available2011-12-21T08:54:10Z
 
dc.date.issued2011
 
dc.description.abstractFibroblast 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.naturelink_to_OA_fulltext
 
dc.identifier.citationJournal 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.doihttp://dx.doi.org/10.1074/jbc.M111.248591
 
dc.identifier.epage34541
 
dc.identifier.hkuros197855
 
dc.identifier.isiWOS:000295406300007
Funding AgencyGrant Number
Research Grant Council of Hong KongHKU3/09C
University of Hong Kong
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.issn0021-9258
2012 Impact Factor: 4.651
2012 SCImago Journal Rankings: 2.723
 
dc.identifier.issue40
 
dc.identifier.pmcidPMC3186365
 
dc.identifier.pmid21846717
 
dc.identifier.scopuseid_2-s2.0-80053428117
 
dc.identifier.spage34533
 
dc.identifier.urihttp://hdl.handle.net/10722/143765
 
dc.identifier.volume286
 
dc.languageeng
 
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Biological Chemistry
 
dc.relation.referencesReferences in Scopus
 
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.
 
dc.rightsThis 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.meshAdipocytes - metabolism
 
dc.subject.meshFibroblast Growth Factors - metabolism
 
dc.subject.meshGlucose Transport Proteins, Facilitative - biosynthesis
 
dc.subject.meshSerum Response Factor - metabolism
 
dc.subject.meshets-Domain Protein Elk-1 - biosynthesis
 
dc.titleFibroblast growth factor 21 induces glucose transporter-1 expression through activation of the serum response factor/Ets-like protein-1 in adipocytes
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong