Mostrar el registro sencillo del ítem

dc.contributor.authorFuster, Jose J. 
dc.contributor.authorZuriaga, María A
dc.contributor.authorZorita, Virginia 
dc.contributor.authorMacLauchlan, Susan
dc.contributor.authorPolackal, Maya N
dc.contributor.authorViana-Huete, Vanesa
dc.contributor.authorFerrer-Pérez, Alba
dc.contributor.authorMatesanz, Nuria 
dc.contributor.authorHerrero-Cervera, Andrea
dc.contributor.authorSano, Soichi
dc.contributor.authorCooper, Matthew A
dc.contributor.authorGonzález-Navarro, Herminia
dc.contributor.authorWalsh, Kenneth
dc.date.accessioned2020-11-04T08:23:07Z
dc.date.available2020-11-04T08:23:07Z
dc.date.issued2020-10-27
dc.identifier.citationCell Rep. 2020; 33(4):108326es_ES
dc.identifier.issn2211-1247
dc.identifier.urihttp://hdl.handle.net/20.500.12105/11280
dc.description.abstractHuman aging is frequently accompanied by the acquisition of somatic mutations in the hematopoietic system that induce clonal hematopoiesis, leading to the development of a mutant clone of hematopoietic progenitors and leukocytes. This somatic-mutation-driven clonal hematopoiesis has been associated with an increased incidence of cardiovascular disease and type 2 diabetes, but whether this epidemiological association reflects a direct, causal contribution of mutant hematopoietic and immune cells to age-related metabolic abnormalities remains unexplored. Here, we show that inactivating mutations in the epigenetic regulator TET2, which lead to clonal hematopoiesis, aggravate age- and obesity-related insulin resistance in mice. This metabolic dysfunction is paralleled by increased expression of the pro-inflammatory cytokine IL-1β in white adipose tissue, and it is suppressed by pharmacological inhibition of NLRP3 inflammasome-mediated IL-1β production. These findings support a causal contribution of somatic TET2 mutations to insulin resistance and type 2 diabetes.es_ES
dc.description.sponsorshipThis work was supported by a grant from the European Foundation for the Study of Diabetes and Lilly European Diabetes Research Programme (to J.J.F.); grants RYC-2016-20026 and RTI2018-093554-A-I00 from the Spanish Ministerio de Ciencia e Innovacion (to J.J.F.); and National Institutes of Health grants HL152174 (to S.S.) and HL139819, HL138014, HL141256, and HL142650 (to K.W.). The project leading to these results also received funding from ‘‘la Caixa’’ Foundation (ID 100010434), under agreement HR17-00267. J.J.F. is a member of the Leducq Foundation Transatlantic Network on Clonal Hematopoiesis and Atherosclerosis and is also supported by a 2019 Leonardo Grant for Researchers and Cultural Creators from the BBVA Foundation, Madrid, Spain. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovacion, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).es_ES
dc.language.isoenges_ES
dc.publisherCell Press es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleTET2-Loss-of-Function-Driven Clonal Hematopoiesis Exacerbates Experimental Insulin Resistance in Aging and Obesity.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.identifier.pubmedID33113366es_ES
dc.format.volume33es_ES
dc.format.number4es_ES
dc.format.page108326es_ES
dc.identifier.doi10.1016/j.celrep.2020.108326es_ES
dc.contributor.funderEuropean Foundation for the Study of Diabetes 
dc.contributor.funderMinisterio de Ciencia e Innovación (España) 
dc.contributor.funderNational Institutes of Health (Estados Unidos) 
dc.contributor.funderFundación La Caixa 
dc.contributor.funderFondation Leducq 
dc.contributor.funderFundación BBVA 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderFundación ProCNIC 
dc.description.peerreviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.celrep.2020.108326es_ES
dc.identifier.journalCell reportses_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RYC-2016-20026es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RTI2018-093554-A-I00es_ES
dc.rights.accessRightsopen accesses_ES


Ficheros en el ítem

Acceso Abierto
Thumbnail
Acceso Abierto
Thumbnail

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem

Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 Internacional