RT Journal Article
T1 Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance.
A1 Martinez-Sanchez, Noelia
A1 Seoane-Collazo, Patricia
A1 Contreras, Cristina
A1 Varela, Luis
A1 Villarroya, Joan
A1 Rial-Pensado, Eva
A1 Buque, Xabier
A1 Aurrekoetxea, Igor
A1 Delgado, Teresa C
A1 Vazquez-Martinez, Rafael
A1 Gonzalez-Garcia, Ismael
A1 Roa, Juan
A1 Whittle, Andrew J
A1 Gomez-Santos, Beatriz
A1 Velagapudi, Vidya
A1 Tung, Y C Loraine
A1 Morgan, Donald A
A1 Voshol, Peter J
A1 Martinez de Morentin, Pablo B
A1 Lopez-Gonzalez, Tania
A1 Liñares-Pose, Laura
A1 Gonzalez, Francisco
A1 Chatterjee, Krishna
A1 Sobrino, Tomas
A1 Medina-Gomez, Gema
A1 Davis, Roger J
A1 Casals, Nuria
A1 Orešič, Matej
A1 Coll, Anthony P
A1 Vidal-Puig, Antonio
A1 Mittag, Jens
A1 Tena-Sempere, Manuel
A1 Malagón, Maria M
A1 Dieguez, Carlos
A1 Martinez-Chantar, Maria Luz
A1 Aspichueta, Patricia
A1 Rahmouni, Kamal
A1 Nogueiras, Ruben
A1 Sabio, Guadalupe
A1 Villarroya, Francesc
A1 Lopez, Miguel
K1 AMPK
K1 BAT
K1 ER stress
K1 JNK1
K1 SF1
K1 VMH
K1 Autonomic nervous system
K1 Ceramides
K1 Liver
K1 Thyroid hormones
AB 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 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.
PB Cell Press
YR 2017
FD 2017-06-15
LK http://hdl.handle.net/10668/11380
UL http://hdl.handle.net/10668/11380
LA en
NO Martínez-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
NO We 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 gruposde 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. andM.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 andMRC_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 InvestigatorAward (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.
DS RISalud
RD Apr 8, 2025