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dc.contributor.authorJimenez, Veronica
dc.contributor.authorJambrina, Claudia
dc.contributor.authorCasana, Estefania
dc.contributor.authorSacristan, Victor
dc.contributor.authorMuñoz, Sergio
dc.contributor.authorDarriba, Sara
dc.contributor.authorRodó, Jordi
dc.contributor.authorMallol, Cristina
dc.contributor.authorGarcia, Miquel
dc.contributor.authorLeón, Xavier
dc.contributor.authorMarcó, Sara
dc.contributor.authorRibera, Albert
dc.contributor.authorElias, Ivet
dc.contributor.authorCasellas, Alba
dc.contributor.authorGrass, Ignasi
dc.contributor.authorElias, Gemma
dc.contributor.authorFerré, Tura
dc.contributor.authorMotas, Sandra
dc.contributor.authorFranckhauser, Sylvie
dc.contributor.authorMulero, Francisca 
dc.contributor.authorNavarro, Marc
dc.contributor.authorHaurigot, Virginia
dc.contributor.authorRuberte, Jesus
dc.contributor.authorBosch, Fatima
dc.date.accessioned2018-11-02T12:41:38Z
dc.date.available2018-11-02T12:41:38Z
dc.date.issued2018-08
dc.identifier.citationEMBO Mol Med. 2018; 10 (8): pii: e8791.es_ES
dc.identifier.issn1757-4676es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6561
dc.description.abstractPrevalence of type 2 diabetes (T2D) and obesity is increasing worldwide. Currently available therapies are not suited for all patients in the heterogeneous obese/T2D population, hence the need for novel treatments. Fibroblast growth factor 21 (FGF21) is considered a promising therapeutic agent for T2D/obesity. Native FGF21 has, however, poor pharmacokinetic properties, making gene therapy an attractive strategy to achieve sustained circulating levels of this protein. Here, adeno-associated viral vectors (AAV) were used to genetically engineer liver, adipose tissue, or skeletal muscle to secrete FGF21. Treatment of animals under long-term high-fat diet feeding or of ob/ob mice resulted in marked reductions in body weight, adipose tissue hypertrophy and inflammation, hepatic steatosis, inflammation and fibrosis, and insulin resistance for > 1 year. This therapeutic effect was achieved in the absence of side effects despite continuously elevated serum FGF21. Furthermore, FGF21 overproduction in healthy animals fed a standard diet prevented the increase in weight and insulin resistance associated with aging. Our study underscores the potential of FGF21 gene therapy to treat obesity, insulin resistance, and T2D.es_ES
dc.description.sponsorshipThis work was supported by grants from Ministerio de Economía y Competi- tividad (MINECO) and FEDER, Plan Nacional I+D+I (SAF2014-54866R), andGeneralitat de Catalunya (2014SGR1669and ICREA Academia Award to F.B.), Spain, from the European Commission (MYOCURE, PHC-14-2015 667751) and the European Foundation for the Study of Diabetes (EFSD/MSD European Research Programme on Novel Therapies for Type 2 Diabetes,2013). V.J. was recipient of a post-doctoral research fellowship from EFSD/ Lilly. E.C., V.S., and C.M. received a predoctoral fellowship from Ministerio de Educación, Cultura y Deporte, and J.R. from Ministerio de Economía y Competitividad, Spain. The authors thank Marta Moya and Maria Molas for technical assistance.es_ES
dc.language.isoenges_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAAV gene therapyes_ES
dc.subjectFGF21es_ES
dc.subjectinsulin resistancees_ES
dc.subjectobesityes_ES
dc.subjecttype 2 diabeteses_ES
dc.titleFGF21 gene therapy as treatment for obesity and insulin resistancees_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID29987000es_ES
dc.format.volume10es_ES
dc.format.number8es_ES
dc.format.pagee8791es_ES
dc.identifier.doi10.15252/emmm.201708791es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.contributor.funderInstitució Catalana de Recerca i Estudis Avançatses_ES
dc.contributor.funderEuropean Foundation for the Study of Diabeteses_ES
dc.contributor.funderFundación Lillyes_ES
dc.contributor.funderGeneralitat de Catalunyaes_ES
dc.description.peerreviewed
dc.identifier.e-issn1757-4684es_ES
dc.relation.publisherversionhttps://doi.org/10.15252/emmm.201708791es_ES
dc.identifier.journalEMBO molecular medicinees_ES
dc.repisalud.institucionCNIOes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2014-54866Res_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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