Adipose-DerivedCirculatingmiRNAsRegulateGeneExpressioninOtherTissuesThomasThomou1,MarceloA.Mori2,JonathanM.Dreyfuss3,6,MasahiroKonishi1,MasajiSakaguchi1,ChristianWolfrum7,TataNageswaraRao1,8,JonathonN.Winnay1,RubenGarcia-Martin1,StevenK.Grinspoon4,PhillipGorden5,andC.RonaldKahn11SectiononIntegrativePhysiology&Metabolism,JoslinDiabetesCenterandHarvardMedicalSchool,Boston,MA2DepartmentofBiochemistryandTissueBiology,StateUniversityofCampinas,Campinas,Brazil3BioinformaticsCore,JoslinDiabetesCenterandHarvardMedicalSchool,Boston,MA4MGHPrograminNutritionalMetabolism,MassachusettsGeneralHospitalandHarvardMedicalSchool,Boston,MA5Diabetes,EndocrinologyandObesityBranch,NIDDK,NationalInstitutesofHealth,Bethesda,MD6DepartmentofBiomedicalEngineering,BostonUniversity,Boston,MA7ETHZ,DepartmentofHealthSciencesandMetabolism,Zurich,Switzerland8DepartmentofBiomedicine,ExperimentalHematology,UniversityHospitalBasel,SwitzerlandAbstractAdiposetissueisamajorsiteofenergystorageandplaysaroleinregulationofmetabolismthroughreleaseofadipokines.Hereweshowthatmicewithafat-specificknockoutofthemiRNA-processingenzymeDicer(ADicerKO),aswellashumanswithlipodystrophy,havemajordecreasesincirculatingexosomalmiRNAs.Transplantationofwhiteandespeciallybrownadiposetissue(BAT)intoADicerKOmicerestorescirculatingmiRNAsassociatedwithanimprovementinglucosetoleranceandareductionofhepaticFGF21mRNAandcirculatingFGF21.Thisgeneregulationcanbemimickedbyadministrationofnormal,butnotAdicerKO,serumexosomes.Expressionofahuman-specificmiRNAinBATofonemouseinvivocanalsoregulateits3’UTR-reporterinliverofanothermousethroughserumexosomaltransfer.Thus,adiposetissueconstitutesamajorsourceofcirculatingexosomalmiRNAs,andthesemiRNAscanregulategeneexpressionindistanttissuestherebyservingasnovelformsofadipokines.Usersmayview,print,copy,anddownloadtextanddata-minethecontentinsuchdocuments,forthepurposesofacademicresearch,subjectalwaystothefullConditionsofuse:http://www.nature.com/authors/editorial_policies/license.html#termsCorrespo...
