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Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease
Qiang Chen1,2; Yuan Jiang1; Yuan An1; Na Zhao1; Yang Zhao1; Chundong Yu1
2011
Source PublicationBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN0006-291X
Volume409Issue:4Pages:651-656
Abstract

Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane tyrosine kinase receptor that plays a crucial role in the regulation of hepatic bile acid and lipid metabolism. FGFR4 underlies high-fat diet-induced hepatic steatosis, suggesting that inhibition of FGFR4 activation may be an effective way to prevent or treat nonalcoholic fatty liver disease (NAFLD). To determine whether neutralization of FGFR4 ligands by soluble FGFR4 extracellular domain (FGFR4-ECD) can inhibit the activation of FGFR4, we constructed FGFR4-ECD expression vector and showed that FGFR4-ECD was effectively expressed in cells and secreted into culture medium. FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling and reduced steatosis of HepG2 induced by palmitic acid in vitro. Furthermore, in a tetracycline-induced fatty liver model, expression of FGFR4-ECD in mouse liver reduced the accumulation of hepatic lipids and partially restored the expression of peroxisome proliferator-activated receptor alpha (PPAR alpha), which promotes the mitochondrial fatty acid beta-oxidation but is repressed by tetracycline. Taken together, these results demonstrate that FGFR4-ECD can block FGFR4 signaling and prevent hepatic steatosis, highlighting the potential value of inhibition of FGFR4 signaling as a method for therapeutic intervention against NAFLD. (C) 2011 Elsevier Inc. All rights reserved.

KeywordFgfr4 Extracellular Domain Nafld Pparα
DOIhttps://doi.org/10.1016/j.bbrc.2011.05.059
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Biophysics
WOS SubjectBiochemistry & Molecular Biology ; Biophysics
WOS IDWOS:000292358500011
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被引频次[WOS]:9   [WOS记录]     [WOS相关记录]
Document TypeJournal article
专题Faculty of Health Sciences
Corresponding AuthorChundong Yu
Affiliation1.State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, China
2.The First Affiliated Hospital of Xiamen University, Xiamen, China
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Qiang Chen,Yuan Jiang,Yuan An,et al. Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2011,409(4):651-656.
APA Qiang Chen,Yuan Jiang,Yuan An,Na Zhao,Yang Zhao,&Chundong Yu.(2011).Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,409(4),651-656.
MLA Qiang Chen,et al."Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 409.4(2011):651-656.
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