Apelin Ameliorates TNF-α-Induced Reduction of Glycogen Synthesis in the Hepatocytes through G Protein-Coupled Receptor APJ.docVIP

Apelin Ameliorates TNF-α-Induced Reduction of Glycogen Synthesis in the Hepatocytes through G Protein-Coupled Receptor APJ.doc

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Apelin Ameliorates TNF-α-Induced Reduction of Glycogen Synthesis in the Hepatocytes through G Protein-Coupled Receptor APJ

ApelinAmelioratesTNF-a-InducedReductionof GlycogenSynthesisintheHepatocytesthroughG Protein-CoupledReceptorAPJ JiaojiaoChu1,3.,HangxiangZhang1,2.,XiuqingHuang1.,YajunLin1,TaoShen1,BeidongChen1., YongMan1,ShuWang1*,JianLi1* 1KeyLaboratoryofGeriatrics,BeijingInstituteofGeriatricsBeijingHospital,MinistryofHealth,Beijing,China,2DepartmentofGerontology,Xi-JingHospital,Fourth MilitaryMedicalUniversity,Xian,China,3ZhejiangHospital,Hangzhou,ZhejiangProvince,China Abstract Apelin,anoveladipokine,isthespecificendogenousligandofGprotein-coupledreceptorAPJ.Consistentwithitsputative roleasanadipokine,apelinhasbeenlinkedtostatesofinsulinresistance.However,thefunctionofapelininhepaticinsulin resistance,avitalpartofinsulinresistance,anditsunderlyingmechanismsstillremainsunclear.Herewedefinetheimpacts ofapelinonTNF-a-inducedreductionofglycogensynthesisinthehepatocytes.Ourstudiesindicatethatapelinreversed TNF-a-inducedreductionofglycogensynthesisinHepG2cells,mouseprimaryhepatocytesandlivertissuesofC57BL/6J micebyimprovingJNK-IRS1-AKT-GSKpathway.Moreover,WesternblotrevealedthatAPJ,butnotapelin,expressedinthe hepatocytesandlivertissuesofmice.WefoundthatF13A,acompetitiveantagonistforGprotein-coupledreceptorAPJ, suppressedtheeffectsofapelinonTNF-a-inducedreductionofglycogensynthesisinthehepatocytes,suggestingAPJis involvedinthefunctionofapelin.Inconclusion,weshownovelevidencesuggestingthatapelinamelioratesTNF-a-induced reductionofglycogensynthesisinthehepatocytesthroughGprotein-coupledreceptorAPJ.Apelinappearsasabeneficial adipokinewithanti-insulinresistanceproperties,andthusasapromisingtherapeutictargetinmetabolicdisorders. Citation:ChuJ,ZhangH,HuangX,LinY,ShenT,etal.(2013)ApelinAmelioratesTNF-a-InducedReductionofGlycogenSynthesisintheHepatocytesthroughG Protein-CoupledReceptorAPJ.PLoSONE8(2):e57231.doi:10.1371/journal.pone.0057231 Editor:GiorgioSesti,UniversitaMagna-GraeciadiCatanzaro,Italy ReceivedSeptember2,2012;AcceptedJanuary18,2013;PublishedFebruary21,2013 Copyright:?2013Chuetal

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