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Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance.

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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.authorTung, Y C Loraine
dc.contributor.authorMorgan, Donald A
dc.contributor.authorVoshol, Peter J
dc.contributor.authorMartinez de Morentin, Pablo B
dc.contributor.authorLopez-Gonzalez, Tania
dc.contributor.authorLiñares-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.authorOrešič, Matej
dc.contributor.authorColl, Anthony P
dc.contributor.authorVidal-Puig, Antonio
dc.contributor.authorMittag, Jens
dc.contributor.authorTena-Sempere, Manuel
dc.contributor.authorMalagón, 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.contributor.funderJunta de Andalucía
dc.contributor.funderInstituto de Salud Carlos III co-funded by FEDER
dc.contributor.funderMinisterio de Economía y Competitividad (MINECO)
dc.contributor.funderEuropean Community’s Seventh Framework Programme
dc.date.accessioned2023-01-25T09:48:33Z
dc.date.available2023-01-25T09:48:33Z
dc.date.issued2017-06-15
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 AMPKα1 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 Vázquez-Martínez. 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 Andalucía (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 investigación del sistema Universitario Vasco (P.A., IT971-16), Generalitat de Catalunya (N.C., 2014SGR465), Fundació La Marató 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 Economía 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), Asociacio´ n Espan˜ ola contra el Ca´ ncer (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 Corporación (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 Ci-MUS 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 ana- € lyses is cordially appreciated. CIBER de Fisiopatologı´a de la Obesidad y Nutrición and CIBER de Enfermedades hepa´ticas 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.description.versionSi
dc.identifier.citationMartínez-Sánchez N, Seoane-Collazo P, Contreras C, Varela L, Villarroya J, Rial-Pensado E, et al. Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance. Cell Metab. 2017 Jul 5;26(1):212-229.e12
dc.identifier.doi10.1016/j.cmet.2017.06.014
dc.identifier.essn1932-7420
dc.identifier.pmcPMC5501726
dc.identifier.pmid28683288
dc.identifier.unpaywallURLhttp://www.cell.com/article/S155041311730356X/pdf
dc.identifier.urihttp://hdl.handle.net/10668/11380
dc.issue.number1
dc.journal.titleCell metabolism
dc.journal.titleabbreviationCell Metab
dc.language.isoen
dc.organizationHospital Universitario Reina Sofía
dc.organizationInstituto Maimónides de Investigación Biomédica de Córdoba-IMIBIC
dc.page.number212-229
dc.publisherCell Press
dc.pubmedtypeJournal Article
dc.relation.projectIDP12-FQM-01943
dc.relation.projectIDRD16/0008/0003
dc.relation.projectIDSAF2014-52223-C2-2-R
dc.relation.projectID260464
dc.relation.projectIDFPU12/01827
dc.relation.publisherversionhttps://linkinghub.elsevier.com/retrieve/pii/S1550-4131(17)30356-X
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAMPK
dc.subjectBAT
dc.subjectER stress
dc.subjectJNK1
dc.subjectSF1
dc.subjectVMH
dc.subjectAutonomic nervous system
dc.subjectCeramides
dc.subjectLiver
dc.subjectThyroid hormones
dc.subject.decsHipotálamo
dc.subject.decsHormonas tiroideas
dc.subject.decsHígado
dc.subject.decsMetabolismo energético
dc.subject.decsMetabolismo de los lípidos
dc.subject.decsProteína quinasa 8 activada por mitógenos
dc.subject.decsRatas Sprague-Dawley
dc.subject.decsTejido adiposo pardo
dc.subject.decsTermogénesis
dc.subject.meshAdipose tissue, brown
dc.subject.meshAnimals
dc.subject.meshEnergy metabolism
dc.subject.meshHypothalamus
dc.subject.meshLipid metabolism
dc.subject.meshLiver
dc.subject.meshMale
dc.subject.meshMice, inbred C57BL
dc.subject.meshMitogen-activated protein kinase 8
dc.subject.meshRats
dc.subject.meshRats, sprague-dawley
dc.subject.meshSignal transduction
dc.subject.meshThermogenesis
dc.subject.meshThyroid hormones
dc.subject.meshTriiodothyronine
dc.titleHypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number26
dspace.entity.typePublication

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