File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Fibroblast growth factor 21 induces glucose transporter-1 expression through activation of the serum response factor/Ets-like protein-1 in adipocytes

TitleFibroblast growth factor 21 induces glucose transporter-1 expression through activation of the serum response factor/Ets-like protein-1 in adipocytes
Authors
Issue Date2011
PublisherAmerican 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?
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.
Persistent Identifierhttp://hdl.handle.net/10722/143765
ISSN
2014 Impact Factor: 4.573
PubMed Central ID
ISI Accession Number ID
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.).

References

 

DC FieldValueLanguage
dc.contributor.authorGe, Xen_HK
dc.contributor.authorChen, Cen_HK
dc.contributor.authorHui, Xen_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorXu, Aen_HK
dc.date.accessioned2011-12-21T08:54:10Z-
dc.date.available2011-12-21T08:54:10Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2011, v. 286 n. 40, p. 34533-34541en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/143765-
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.en_HK
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
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 adipocytesen_HK
dc.typeArticleen_HK
dc.identifier.emailWang, Y: yuwanghk@hku.hken_HK
dc.identifier.emailLam, KSL: ksllam@hku.hken_HK
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.authorityWang, Y=rp00239en_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M111.248591en_HK
dc.identifier.pmid21846717en_HK
dc.identifier.pmcidPMC3186365-
dc.identifier.scopuseid_2-s2.0-80053428117en_HK
dc.identifier.hkuros197855en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80053428117&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume286en_HK
dc.identifier.issue40en_HK
dc.identifier.spage34533en_HK
dc.identifier.epage34541en_HK
dc.identifier.isiWOS:000295406300007-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridGe, X=53867813200en_HK
dc.identifier.scopusauthoridChen, C=53867897200en_HK
dc.identifier.scopusauthoridHui, X=26666795900en_HK
dc.identifier.scopusauthoridWang, Y=34973733700en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats