Hypothalamic AMPK-ER Stress-JNK1 axis mediates the central actions of thyroid hormones on energy balance
Author
Publication date
2017-07ISSN
1932-7420
Abstract
Thyroid 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.
Document Type
Article
Document version
Accepted version
Language
English
Subject (CDU)
61 - Medical sciences
Keywords
Pages
31
Publisher
Elsevier
Collection
26; 1
Is part of
Cell Metabolism
Recommended citation
Martinez-Sanchez, Noelia; Seoane-Collazo, Patricia; Contreras, Cristina [et al.]. Hypothalamic AMPK-ER Stress-JNK1 axis mediates the central actions of thyroid hormones on energy balance. Cell Metabolism, 2017, 26(1), p. 212-229. Disponible en: <https://www.cell.com/cell-metabolism/fulltext/S1550-4131(17)30356-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS155041311730356X%3Fshowall%3Dtrue>. Fecha de acceso: 25 may. 2020. DOI: 10.1016/j.cmet.2017.06.014.
Grant agreement number
info:eu-repo/grantAgreement/ES/1PE/SAF2014-52223-C2-2-R
info:eu-repo/grantAgreement/ES/1PE/BFU2014-57581-P
info:eu-repo/grantAgreement/ES/1PE/BFU2013-44229-R
info:eu-repo/grantAgreement/ES/1PE/BFU2014-55871-P
info:eu-repo/grantAgreement/ES/1PE/SAF2014-54658-R
info:eu-repo/grantAgreement/ES/1PE/SAF2015-64352-R
info:eu-repo/grantAgreement/ES/1PE/BFU2015-70664R
info:eu-repo/grantAgreement/ES/1PE/SAF2013-43506-R
info:eu-repo/grantAgreement/ES/1PE/SAF2014 55725
info:eu-repo/grantAgreement/ES/1PE/SAF2015-71026-R
info:eu-repo/grantAgreement/ES/1PE/BFU2015-70454-REDT/Adipoplast
info:eu-repo/grantAgreement/ES/1PE/IJDC-2014-19681
info:eu-repo/grantAgreement/ES/1PE/BES-2015-072743
info:eu-repo/grantAgreement/ES/1PE/SEV-2015-0505
info:eu-repo/grantAgreement/EC/FP7/260464/EU
info:eu-repo/grantAgreement/EC/FP7/281854/EU
Note
We dedicate this work to the bright memory of our colleague and friend Rafael Vazquez-Martınez. The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreements n260464 – the OBECAN project (G.S.) and n 281854 – the ObERStress project (M.L.), Xunta de Galicia (F.G., ED431C2016-025 and ED341D-R2016-032; R.N., 2015-CP080 and 2016-PG057; M.L., 2015-CP079 and 2016-PG068), Junta de Andalucı´a (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 Economı´a 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 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 SEV2015-0505). 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 Nutricio´ n 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.
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- Ciències de la Salut [980]
Rights
© 2017 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-nd/4.0/
