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dc.contributor.authorCioffi, Michele
dc.contributor.authorVallespinos-Serrano, Mireia
dc.contributor.authorTrabulo, Sara M.
dc.contributor.authorJose Fernandez-Marcos, Pablo
dc.contributor.authorFirment, Ashley N.
dc.contributor.authorVazquez, Berta N.
dc.contributor.authorVieira, Catarina R.
dc.contributor.authorMulero, Francisca 
dc.contributor.authorCamara, Juan A.
dc.contributor.authorCronin, Ultan P.
dc.contributor.authorPerez, Manuel
dc.contributor.authorSoriano, Joaquim
dc.contributor.authorGalvez, Beatriz G. 
dc.contributor.authorCastells-Garcia, Alvaro
dc.contributor.authorHaage, Verena
dc.contributor.authorRaj, Deepak
dc.contributor.authorMegias Vazquez, Diego 
dc.contributor.authorHahn, Stephan
dc.contributor.authorSerrano, Lourdes
dc.contributor.authorMoon, Anne
dc.contributor.authorAicher, Alexandra
dc.contributor.authorHeeschen, Christopher 
dc.date.accessioned2017-11-27T13:49:49Z
dc.date.available2017-11-27T13:49:49Z
dc.date.issued2015
dc.identifierISI:000360965500009
dc.identifier.citationCell Rep. 2015; 12(10):1594-605
dc.identifier.issn2211-1247
dc.identifier.urihttp://hdl.handle.net/20.500.12105/5390
dc.description.abstractConquering obesity has become a major socioeconomic challenge. Here, we show that reduced expression of the miR-25-93-106b cluster, or miR-93 alone, increases fat mass and, subsequently, insulin resistance. Mechanistically, we discovered an intricate interplay between enhanced adipocyte precursor turnover and increased adipogenesis. First, miR-93 controls Tbx3, thereby limiting self-renewal in early adipocyte precursors. Second, miR-93 inhibits the metabolic target Sirt7, which we identified as a major driver of in vivo adipogenesis via induction of differentiation and maturation of early adipocyte precursors. Using mouse parabiosis, obesity in mir-25-93-106b(-/-) mice could be rescued by restoring levels of circulating miRNA and subsequent inhibition of Tbx3 and Sirt7. Downregulation of miR-93 also occurred in obese ob/ob mice, and this phenocopy of mir-25-93-106b(-/-) was partially reversible with injection of miR-93 mimics. Our data establish miR-93 as a negative regulator of adipogenesis and a potential therapeutic option for obesity and the metabolic syndrome.
dc.description.sponsorshipWe graciously thank Flor Diaz for expert technical assistance. We are grateful to Andrea Ventura for providing the mir-25-93-106b<SUP>-/-</SUP> mice and Elena Lopez-Guadamillas for providing visceral fad pads from ob/ob mice. Research was supported by the European Research Council Advanced Investigator Grant (Pa-CSC 233460) and the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreements 256974 (EPC-TM-NET) and 602783 (CAM-PaC). M.C. was supported by a La Caixa Fellowship.
dc.language.isoeng
dc.publisherCELL PRESS
dc.relation.isversionofPublisher's version
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectADIPOCYTE DIFFERENTIATION
dc.subjectSTEM-CELLS
dc.subjectINSULIN-RESISTANCE
dc.subjectIN-VIVO
dc.subjectTISSUE
dc.subjectIDENTIFICATION
dc.subjectREGULATOR
dc.subjectOBESITY
dc.subjectGROWTH
dc.subjectRISK
dc.titleMiR-93 Controls Adiposity via Inhibition of Sirt7 and Tbx3
dc.typeArtículo
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.identifier.pubmedID26321631
dc.format.volume12
dc.format.page1594-1605
dc.identifier.doi10.1016/j.celrep.2015.08.006
dc.contributor.funderEuropean Research Council [Pa-CSC 233460]
dc.contributor.funder7º Programa Marco - Comisión Europea [256974, 602783]
dc.contributor.funderLa Caixa Fellowship
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1016/j.celrep.2015.08.006
dc.identifier.journalCell Reports
dc.repisalud.orgCNICCNIC::Grupos de investigación::Antiguos CNIC
dc.repisalud.institucionCNIC
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/256974/EUes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/602783/EUes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/233460/EUes_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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