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dc.contributor.authorMartinez-Sanchez, Noelia
dc.contributor.authorSeoane-Collazo, Patricia
dc.contributor.authorContreras, Cristina
dc.contributor.authorVarela, Luis
dc.contributor.authorVillarroya, Joan
dc.contributor.authorRial-Pensado, Eva
dc.contributor.authorBuque, Xabier
dc.contributor.authorAurrekoetxea, Igor
dc.contributor.authorDelgado, Teresa C.
dc.contributor.authorVazquez-Martinez, Rafael
dc.contributor.authorGonzalez-Garcia, Ismael
dc.contributor.authorRoa, Juan
dc.contributor.authorWhittle, Andrew J.
dc.contributor.authorGomez-Santos, Beatriz
dc.contributor.authorVelagapudi, Vidya
dc.contributor.authorLoraine Tung, Y. C.
dc.contributor.authorMorgan, Donald A.
dc.contributor.authorVoshol, Peter J.
dc.contributor.authorMartinez de Morentin, Pablo B.
dc.contributor.authorLopez-Gonzalez, Tania
dc.contributor.authorLinares-Pose, Laura
dc.contributor.authorGonzalez, Francisco
dc.contributor.authorChatterjee, Krishna
dc.contributor.authorSobrino, Tomas
dc.contributor.authorMedina-Gomez, Gema
dc.contributor.authorDavis, Roger J.
dc.contributor.authorCasals, Nuria
dc.contributor.authorOresic, Matej
dc.contributor.authorColl, Anthony P.
dc.contributor.authorVidal-Puig, Antonio
dc.contributor.authorMittag, Jens
dc.contributor.authorTena-Sempere, Manuel
dc.contributor.authorMalagon, Maria M.
dc.contributor.authorDieguez, Carlos
dc.contributor.authorMartinez-Chantar, Maria Luz
dc.contributor.authorAspichueta, Patricia
dc.contributor.authorRahmouni, Kamal
dc.contributor.authorNogueiras, Ruben
dc.contributor.authorSabio, Guadalupe 
dc.contributor.authorVillarroya, Francesc
dc.contributor.authorLopez, Miguel
dc.date.accessioned2018-10-19T08:00:44Z
dc.date.available2018-10-19T08:00:44Z
dc.date.issued2017
dc.identifierISI:000404885800023
dc.identifier.citationCell Metab. 2017; 26(1):212-229 e12
dc.identifier.issn1550-4131
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6501
dc.description.abstractThyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum(ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPK alpha 1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.
dc.description.sponsorshipWe dedicate this work to the bright memory of our colleague and friend Rafael Vazquez-Martinez. The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreements no 260464 - the OBECAN project (G.S.) and no 281854 - the ObERStress project (M.L.), Xunta de Galicia (F.G., ED431C-2016-025 and ED341D-R2016-032; R.N., 2015-CP080 and 2016-PG057; M.L., 2015-CP079 and 2016-PG068), Junta de Andalucia (M.T.-S., P12-FQM-01943), Gobierno Vasco-Departamento de Salud (M.L.M.-C., 2013111114), EITB (M.L.M.-C., BIO15/CA/014), Ayudas para apoyar grupos de investigacion del sistema Universitario Vasco (P.A., IT971-16), Generalitat de Catalunya (N.C., 2014SGR465), Fundacio La Marato de TV3 (N.C., 87/C/2016), Instituto de Salud Carlos III co-funded by FEDER (F.G., RD16/0008/ 0003; M.L.M.-C., PIE14/00031), Ministerio de Economia y Competitividad (MINECO) co-funded by the FEDER Program of EU (N.C., SAF2014-52223-C2-2-R; M.T.-S., BFU2014-57581-P -P; M.M.M., BFU2013-44229-R; C.D., BFU2014-55871-P; M.L.M.-C., SAF2014-54658-R; P.A., SAF2015-64352-R; R.N., BFU2015-70664R; G.S., SAF2013-43506-R; F.V., SAF2014 55725; M.L., SAF2015-71026-R; G.M., M.M.M., F.V., and M.L., BFU2015-70454-REDT/Adipoplast), Asociacion Espanola contra el Cancer (T.C.D. and M.L.M.-C.), Medical Research Council (MRC) Metabolic Diseases Unit (A.J.W., Y.C.L.T., A.P.C., and A.V.-P., MRC\_MC\_UU\_12012/1 and MRC\_UU\_12015/5), MRC Programme Grant (Y.C.L.T. and A.P.C., G9824984), MRC Disease Model Core (P.J.V. and A. V.-P.), Wellcome Trust Investigator Award (K.C., 095564/Z/11/Z), Deutsche Forschungsgemeinschaft (J.M., Mi1242/2-1), NIH (R.J.D., DK107220 and DK112698; K.R., HL084207), American Heart Association (K.R., EIA\#14EIA18860041) and the University of Iowa Fraternal Order of Eagles Diabetes Research Center (K.R.), EFSD/Lilly Programme (G.S., GIM/EFS1601), Astra Zeneca Foundation (R.N.) and the European Foundation for the Study of Diabetes (R.N.), and Atresmedia Corporacion (M.L.). C.C. is recipient of a Sara Borrell Contract (CD14/0007) from ISCIII; J.V. is recipient of a Juan de la Cierva Contract (IJDC-2014-19681) from MINECO; E.R.-P. is recipient of a fellowship from MINECO (BES-2015-072743); I. G.-G. is recipient of a fellowship from MINECO (FPU12/01827); L.L.-P. is recipient of a fellowship from Xunta de Galicia (ED481A-2016/094); T.C.D. is supported by AECC (AIO2013); T.S. is recipient of a Miguel Servet Contract (CP12/03121) from ISCIII; R.J.D. is an Investigator of the Howard Hughes Medical Institute; and F.V. is an ICREA Academia researcher, Generalitat de Catalunya. The CiMUS is supported by the Xunta de Galicia (2016-2019, ED431G/05) and the CNIC is supported by the MINECO and the Pro-CNIC Foundation. Pro-CNIC Foundation is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). The technical assistance of Luz Casas in performing the in situ hybridization, Maria Jesus Sanchez-Tapia in performing genotyping analyses, and Tuulikki Seppanen-Laakso and Ulla Lahtinen in performing lipidomics analyses is cordially appreciated. CIBER de Fisiopatologia de la Obesidad y Nutricion and CIBER de Enfermedades hepaticas y Digestivas are initiatives of ISCIII. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.language.isoeng
dc.publisherCell Press 
dc.type.hasVersionVoR
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectDIET-INDUCED OBESITY
dc.subjectADIPOSE-TISSUE THERMOGENESIS
dc.subjectRAT-LIVER
dc.subjectINSULIN-RESISTANCE
dc.subjectVLDL SECRETION
dc.subjectBROWN FAT
dc.subjectNEURONS
dc.subjectMETABOLISM
dc.subjectRECEPTOR
dc.subjectHOMEOSTASIS
dc.titleHypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance
dc.typejournal article
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.identifier.pubmedID28683288
dc.format.volume26
dc.format.page212+
dc.identifier.doi10.1016/j.cmet.2017.06.014
dc.contributor.funderUnión Europea. Comisión Europea 
dc.contributor.funderXunta de Galicia (España) 
dc.contributor.funderRegional Government of Andalusia (España) 
dc.contributor.funderBasque Government (España) 
dc.contributor.funderEITB - Radio Televisión Pública Vasca 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderGovernment of Catalonia (España) 
dc.contributor.funderFundación La Marató TV3 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderAsociación Española Contra el Cáncer 
dc.contributor.funderMedical Research Council (Reino Unido) 
dc.contributor.funderWellcome Trust 
dc.contributor.funderDeutsche Forschungsgemeinschaft (Alemania) 
dc.contributor.funderNational Institutes of Health (Estados Unidos) 
dc.contributor.funderAmerican Heart Association 
dc.contributor.funderFraternal Order of Eagles (Estados Unidos) 
dc.contributor.funderEuropean Foundation for the Study of Diabetes 
dc.contributor.funderFundación AstraZeneca 
dc.contributor.funderAtresmedia 
dc.contributor.funderFundación ProCNIC 
dc.contributor.funderUniversity of Iowa (Estados Unidos) 
dc.description.peerreviewedSí
dc.identifier.e-issn1932-7420
dc.relation.publisherversionhttps://doi.org/10.1016/j.cmet.2017.06.014
dc.identifier.journalCell Metabolism
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.institucionCNIC
dc.relation.projectIDMINECO/ICTI2013-2016/SAF2014-52223-C2-2-Res_ES
dc.relation.projectIDMINECO/ICTI2013-2016/BFU2014-57581-Pes_ES
dc.relation.projectIDMINECO/ICTI2013-2016/BFU2013-44229-Res_ES
dc.relation.projectIDMINECO/ICTI2013-2016/BFU2014-55871-Pes_ES
dc.relation.projectIDMINECO/ICTI2013-2016/SAF2014-54658-Res_ES
dc.relation.projectIDMINECO/ICTI2013-2016/SAF2015-64352-Res_ES
dc.relation.projectIDMINECO/ICTI2013-2016/BFU2015-70664Res_ES
dc.relation.projectIDMINECO/ICTI2013-2016/SAF2013-43506-Res_ES
dc.relation.projectIDMINECO/ICTI2013-2016/SAF2014 55725es_ES
dc.relation.projectIDMINECO/ICTI2013-2016/SAF2015-71026-Res_ES
dc.relation.projectIDMINECO/ICTI2013-2016/BFU2015-70454-REDT/Adipoplastes_ES
dc.relation.projectIDMINECO/ICTI2013-2016/IJDC-2014-19681es_ES
dc.relation.projectIDMINECO/ICTI2013-2016/BES-2015-072743es_ES
dc.relation.projectIDMINECO/ICTI2013-2016/FPU12/01827es_ES
dc.relation.projectIDMINECO/ICTI2013-2016/SEV-2015-0505es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/260464/EUes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/281854/EUes_ES
dc.rights.accessRightsopen accesses_ES


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