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dc.contributor.authorMatesanz, Nuria 
dc.contributor.authorBernardo, Edgar 
dc.contributor.authorAcin-Perez, Rebeca 
dc.contributor.authorManieri, Elisa 
dc.contributor.authorPerez-Sieira, Sonia
dc.contributor.authorHernandez-Cosido, Lourdes
dc.contributor.authorMontalvo-Romeral, Valle 
dc.contributor.authorMora, Alfonso 
dc.contributor.authorRodriguez, Elena 
dc.contributor.authorLeiva-Vega, Luis 
dc.contributor.authorLechuga-Vieco, Ana V. 
dc.contributor.authorRuiz-Cabello, Jesus 
dc.contributor.authorTorres, Jorge L
dc.contributor.authorCrespo-Ruiz, Maria 
dc.contributor.authorCenteno, Francisco
dc.contributor.authorAlvarez, Clara V.
dc.contributor.authorMarcos, Miguel
dc.contributor.authorEnriquez, José Antonio 
dc.contributor.authorNogueiras, Ruben
dc.contributor.authorSabio, Guadalupe 
dc.date.accessioned2018-10-19T08:00:42Z
dc.date.available2018-10-19T08:00:42Z
dc.date.issued2017
dc.identifierISI:000412775200008
dc.identifier.citationNat Commun. 2017; 8(1):856
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6494
dc.description.abstractIncreasing the thermogenic capacity of adipose tissue to enhance organismal energy expenditure is considered a promising therapeutic strategy to combat obesity. Here, we report that expression of the p38 MAPK activator MKK6 is elevated in white adipose tissue of obese individuals. Using knockout animals and shRNA, we show that Mkk6 deletion increases energy expenditure and thermogenic capacity of white adipose tissue, protecting mice against diet-induced obesity and the development of diabetes. Deletion of Mkk6 increases T3-stimulated UCP1 expression in adipocytes, thereby increasing their thermogenic capacity. Mechanistically, we demonstrate that, in white adipose tissue, p38 is activated by an alternative pathway involving AMPK, TAK, and TAB. Our results identify MKK6 in adipocytes as a potential therapeutic target to reduce obesity.
dc.description.sponsorshipWe thank S. Bartlett for English editing. We are grateful to R.J. Davis for critical reading of the manuscript and R. Gonzalez-Sarmiento for help with clinical study design. We thank the staff at the CNIC Animal facility and S. Perez-Romero for technical assistance. G.S. and R.A.-P. are investigators of the Ramon y Cajal Program. E.M. was a Caixa fellow, and V.M.-R. and E.B. were FPI (FPI BES-2014-069332 and FPI BES-2011-043428, respectively). This work was funded by the following grants supported in part by funds from European Regional Development Fund (ERDF-FEDER): to G.S.: funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. ERC 260464, EFSD/Lilly, MINECO-FEDER SAF2016-79126-R, and Comunidad de Madrid S2010/BMD-2326; to M.M.: ISCIII and FEDER, PI10/01692, and I3SNS-INT12/049; to L.H.-C.: Junta de Castilla y Leon GRS 681/A/11; to R.N.: MINECO BFU2015-70664-R, Xunta de Galicia 2015-CP080 and PIE13/00024, and ERC281408; European grants UE0/MCA1108 and UE0/MCA1201; and the Comunidad de Madrid CAM/API1009; to F.C.: Junta de Extremadura-FEDER BR15164; to C.V.A. BFU2013-46109-R. The CNIC is supported by the Ministry of Economy, Industry and Competitiveness (MEIC) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).
dc.language.isoeng
dc.publisherNATURE PUBLISHING GROUP
dc.relation.isversionofPublisher's version
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectACTIVATED PROTEIN-KINASE
dc.subjectBODY-MASS INDEX
dc.subjectINSULIN-RESISTANCE
dc.subjectADULT HUMANS
dc.subjectADAPTIVE THERMOGENESIS
dc.subjectHUMAN ADIPOCYTES
dc.subjectTHYROID-FUNCTION
dc.subjectMAP KINASE
dc.subjectFAT
dc.subjectGENE
dc.titleMKK6 controls T3-mediated browning of white adipose tissue
dc.typeArtículo
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID29021624
dc.format.volume8
dc.identifier.doi10.1038/s41467-017-00948-z
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)
dc.contributor.funderEuropean Research Council
dc.contributor.funderEuropean Foundation for the Study of Diabetes
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España)
dc.contributor.funderComunidad de Madrid
dc.contributor.funderInstituto de Salud Carlos III - ISCIII
dc.contributor.funderJunta de Castilla y León
dc.contributor.funderXunta de Galicia
dc.contributor.funderJunta de Extremadura
dc.contributor.funderFundación ProCNIC
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1038/s41467-017-00948-z
dc.identifier.journalNATURE COMMUNICATIONS
dc.repisalud.orgCNICCNIC::Grupos de investigación::Papel de las quinasas activadas por el estrés en el desarrollo de enfermedades cardiovasculares, diabetes y cáncer
dc.repisalud.orgCNICCNIC::Grupos de investigación::Genética Funcional del Sistema de Fosforilación Oxidativa
dc.repisalud.institucionCNIC
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/260464/EUes_ES
dc.relation.projectIDMINECO/ICTI2013-2016/SEV-2015-0505es_ES
dc.relation.projectIDMINECO/ICTI2013-2016/SAF-2016-79126-Res_ES
dc.relation.projectIDMINECO/ICTI2013-2016/BFU-2015-70664-Res_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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