Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles 英文参考文献.docVIP

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Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles 英文参考文献.doc

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Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles 英文参考文献

ErythropoietinOver-ExpressionProtectsagainstDiet- InducedObesityinMicethroughIncreasedFatOxidation inMuscles PernilleHojman1,2*,CamillaBrolin2,HanneGissel3,ClausBrandt1,BoZerahn4,BenteKlarlund Pedersen1,JulieGehl2* 1CentreofInflammationandMetabolismattheDepartmentofInfectiousDiseases,Rigshospitalet,UniversityofCopenhagen,Copenhagen,Denmark,2Departmentof Oncology,CopenhagenUniversityHospitalHerlev,Herlev,Denmark,3DepartmentofPhysiologyandBiophysics,UniversityofAarhus,Aarhus,Denmark,4Departmentof ClinicalPhysiologyandNuclearMedicine,CopenhagenUniversityHospitalHerlev,Herlev,Denmark Abstract Erythropoietincanbeover-expressedinskeletalmusclesbygeneelectrotransfer,resultingin100-foldincreaseinserumEPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney patients. Thus we applied the EPO over-expression model to investigatethemetaboliceffectofEPOinvivo. At12weeks,EPOexpressionresultedina23%weightreduction(P,0.01) in EPOtransfected obesemice; thus themice weighed 21.960.8g(control,normaldiet,) 21.961.4g(EPO,normal diet), 35.363.3g(control,high-fatdiet)and28.862.6g(EPO,high-fatdiet).Correspondingly, DXAscanningrevealedthatthis wasduetoa28%reductioninadiposetissuemass. Thedecreaseinadiposetissuemasswasaccompaniedbyacomplete normalisationoffastinginsulinlevelsandglucosetoleranceinthehigh-fatfedmice.EPOexpressionalsoinduceda14% increaseinmusclevolumeanda25%increaseinvascularisationoftheEPOtransfectedmuscle.Muscleforceandstamina werenotaffectedbyEPOexpression.PCRarrayanalysisrevealedthatgenesinvolvedinlipidmetabolism,thermogenesis andinflammationwereincreasedinmusclesinresponsetoEPOexpression,whilegenesinvolvedinglucosemetabolism were down-regulated. In addition, muscular fat oxidation was increased 1.8-fold in both the EPO transfected and contralateralmuscles. Inconclusion,wehaveshownthatEPOwhenexpressedinsupra-physiologicallevelshassubstant