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Article: Growth hormone induces hepatic production of fibroblast growth factor 21 through a mechanism dependent on lipolysis in adipocytes

TitleGrowth hormone induces hepatic production of fibroblast growth factor 21 through a mechanism dependent on lipolysis 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. 34559-34566 How to Cite?
AbstractFibroblast growth factor (FGF) 21 and growth hormone (GH) are metabolic hormones that play important roles in regulating glucose and lipid metabolism. Both hormones are induced in response to fasting and exert their actions on adipocytes to regulate lipolysis. However, the molecular interaction between these two hormones remains unclear. Here we demonstrate the existence of a feedback loop between GH and FGF21 on the regulation of lipolysis in adipocytes. A single bolus injection of GH into C57 mice acutely increases both mRNA and protein expression of FGF21 in the liver, thereby leading to a marked elevation of serum FGF21 concentrations. Such a stimulatory effect of GH on hepatic FGF21 production is abrogated by pre-treatment of mice with the lipolysis inhibitor niacin. Direct incubation of either liver explants or human HepG2 hepatocytes with GH has no effect on FGF21 expression. On the other hand, FGF21 production in HepG2 cells is significantly induced by incubation with the conditioned medium harvested from GHtreated adipose tissue explants, which contains high concentrations of free fatty acids (FFA). Further analysis shows that FFA released by GH-induced lipolysis stimulates hepatic FGF21 expression by activation of the transcription factor PPARα. In FGF21-null mice, both the magnitude and duration of GH-induced lipolysis are significantly higher than those in their wild type littermates. Taken together, these findings suggest that GH-induced hepatic FGF21 production is mediated by FFA released from adipose tissues, and elevated FGF21 in turn acts as a negative feedback signal to terminate GH-stimulated lipolysis in adipocytes. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/143762
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council of Hong KongHKU3/CRF/09
University of Hong Kong2011CB504004
Funding Information:

This work was supported by the Collaborative Research Fund (HKU3/CRF/09), from the Research Grant Council of Hong Kong, seeding fund for basic research and the matching fund for the National Basic Research Program of China (Project no: 2011CB504004) from the University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorChen, Wen_HK
dc.contributor.authorHoo, RLCen_HK
dc.contributor.authorKonishi, Men_HK
dc.contributor.authorItoh, Nen_HK
dc.contributor.authorLee, PCen_HK
dc.contributor.authorYe, HYen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorXu, Aen_HK
dc.date.accessioned2011-12-21T08:54:06Z-
dc.date.available2011-12-21T08:54:06Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2011, v. 286 n. 40, p. 34559-34566en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/143762-
dc.description.abstractFibroblast growth factor (FGF) 21 and growth hormone (GH) are metabolic hormones that play important roles in regulating glucose and lipid metabolism. Both hormones are induced in response to fasting and exert their actions on adipocytes to regulate lipolysis. However, the molecular interaction between these two hormones remains unclear. Here we demonstrate the existence of a feedback loop between GH and FGF21 on the regulation of lipolysis in adipocytes. A single bolus injection of GH into C57 mice acutely increases both mRNA and protein expression of FGF21 in the liver, thereby leading to a marked elevation of serum FGF21 concentrations. Such a stimulatory effect of GH on hepatic FGF21 production is abrogated by pre-treatment of mice with the lipolysis inhibitor niacin. Direct incubation of either liver explants or human HepG2 hepatocytes with GH has no effect on FGF21 expression. On the other hand, FGF21 production in HepG2 cells is significantly induced by incubation with the conditioned medium harvested from GHtreated adipose tissue explants, which contains high concentrations of free fatty acids (FFA). Further analysis shows that FFA released by GH-induced lipolysis stimulates hepatic FGF21 expression by activation of the transcription factor PPARα. In FGF21-null mice, both the magnitude and duration of GH-induced lipolysis are significantly higher than those in their wild type littermates. Taken together, these findings suggest that GH-induced hepatic FGF21 production is mediated by FFA released from adipose tissues, and elevated FGF21 in turn acts as a negative feedback signal to terminate GH-stimulated lipolysis in adipocytes. © 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.en_US
dc.rightsThis research was originally published in Journal of Biological Chemistry. Wei Chen, Ruby Lai-chong Hoo, Morichika Konishi, Nobuyuki Itoh, Pui-chi Lee, Hong-ying Ye, Karen Siu-ling Lam and Aimin Xu. Growth hormone induces hepatic production of fibroblast growth factor 21 through a mechanism dependent on lipolysis in adipocytes. Journal of Biological Chemistry. 2011. Vol 286:pp34559-pp34566. © the American Society for Biochemistry and Molecular Biologyen_US
dc.subject.meshFibroblast Growth Factors - biosynthesisen_US
dc.subject.meshGene Expression Regulationen_US
dc.subject.meshGrowth Hormone - metabolismen_US
dc.subject.meshHuman Growth Hormone - metabolismen_US
dc.subject.meshLiver - metabolismen_US
dc.titleGrowth hormone induces hepatic production of fibroblast growth factor 21 through a mechanism dependent on lipolysis in adipocytesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9258&volume=286&spage=34559&epage=34566&date=2011&atitle=Growth+Hormone+Induces+Hepatic+Production+Of+Fibroblast+Growth+Factor+21+Through+A+Mechanism+Dependent+On+Lipolysis+In+Adipocytes.en_US
dc.identifier.emailHoo, RLC:rubyhoo@hkucc.hku.hken_HK
dc.identifier.emailLam, KSL:ksllam@hku.hken_HK
dc.identifier.emailXu, A:amxu@hkucc.hku.hken_HK
dc.identifier.authorityHoo, RLC=rp01334en_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M111.285965en_HK
dc.identifier.pmid21849508-
dc.identifier.pmcidPMC3186378en_US
dc.identifier.scopuseid_2-s2.0-80053409251en_HK
dc.identifier.hkuros197844en_US
dc.identifier.hkuros226367-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80053409251&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume286en_HK
dc.identifier.issue40en_HK
dc.identifier.spage34559en_HK
dc.identifier.epage34566en_HK
dc.identifier.isiWOS:000295406300010-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChen, W=36012609700en_HK
dc.identifier.scopusauthoridHoo, RLC=6602369766en_HK
dc.identifier.scopusauthoridKonishi, M=7201685732en_HK
dc.identifier.scopusauthoridItoh, N=7401590949en_HK
dc.identifier.scopusauthoridLee, PC=53865048500en_HK
dc.identifier.scopusauthoridYe, HY=7201887749en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK

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