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dc.contributor.author | Fuster, Jose J. | |
dc.contributor.author | Zuriaga, María A | |
dc.contributor.author | Zorita, Virginia | |
dc.contributor.author | MacLauchlan, Susan | |
dc.contributor.author | Polackal, Maya N | |
dc.contributor.author | Viana-Huete, Vanesa | |
dc.contributor.author | Ferrer-Pérez, Alba | |
dc.contributor.author | Matesanz, Nuria | |
dc.contributor.author | Herrero-Cervera, Andrea | |
dc.contributor.author | Sano, Soichi | |
dc.contributor.author | Cooper, Matthew A | |
dc.contributor.author | González-Navarro, Herminia | |
dc.contributor.author | Walsh, Kenneth | |
dc.date.accessioned | 2020-11-04T08:23:07Z | |
dc.date.available | 2020-11-04T08:23:07Z | |
dc.date.issued | 2020-10-27 | |
dc.identifier.citation | Cell Rep. 2020; 33(4):108326 | es_ES |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/11280 | |
dc.description.abstract | Human 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.sponsorship | This 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.iso | eng | es_ES |
dc.publisher | Cell Press | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | TET2-Loss-of-Function-Driven Clonal Hematopoiesis Exacerbates Experimental Insulin Resistance in Aging and Obesity. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 33113366 | es_ES |
dc.format.volume | 33 | es_ES |
dc.format.number | 4 | es_ES |
dc.format.page | 108326 | es_ES |
dc.identifier.doi | 10.1016/j.celrep.2020.108326 | es_ES |
dc.contributor.funder | European Foundation for the Study of Diabetes | |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | |
dc.contributor.funder | National Institutes of Health (Estados Unidos) | |
dc.contributor.funder | Fundación La Caixa | |
dc.contributor.funder | Fondation Leducq | |
dc.contributor.funder | Fundación BBVA | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Fundación ProCNIC | |
dc.description.peerreviewed | Sí | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.celrep.2020.108326 | es_ES |
dc.identifier.journal | Cell reports | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SEV-2015-0505 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RYC-2016-20026 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RTI2018-093554-A-I00 | es_ES |
dc.rights.accessRights | open access | es_ES |