Hypothalamic AMPK-ER Stress-JNK1 axis mediates the central actions of thyroid hormones on energy balance
Author
Martinez-Sanchez, Noelia
Seoane-Collazo, Patricia
Contreras, Cristina
Varela, Luis
Villarroya, Joan
Rial-Pensado, Eva
Buque, Xabier
Aurrekoetxea, Igor
Delgado, Teresa C.
Vazquez-Martinez, Rafael
Gonzalez-Garcia, Ismael
Roa, Juan
Whittle, Andrew J.
Gomez-Santos, Beatriz
Velagapudi, Vidya
Loraine Tung, Y. C.
Morgan, Donald A.
Voshol, Peter J.
Martinez de Morentin, Pablo B.
Lopez-Gonzalez, Tania
Linares-Pose, Laura
Gonzalez, Francisco
Chatterjee, Krishna
Sobrino, Tomas
Medina-Gomez, Gema
Davis, Roger J.
Casals i Farré, Núria
Oresic, Matej
Coll, Anthony P.
Vidal-Puig, Antonio
Mittag, Jens
Tena-Sempere, Manuel
Malagon, Maria M.
Dieguez, Carlos
Martinez-Chantar, Maria Luz
Aspichueta, Patricia
Rahmouni, Kamal
Nogueiras, Rubén
Sabio, Guadalupe
Villarroya, Francesc
Lopez, Miguel
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
Obesitat
Teixit adipós
Insulinoresistència
Neurones
Metabolisme
Obesidad
Tejido adiposo
Resistencia a la insulina
Neuronas
Metabolismo
Obesity
Adipose tissue
Insulin resistance
Neurons
Metabolism
Pages
31
Publisher
Elsevier
Collection
26;1
Is part of
Cell Metabolism
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
This item appears in the following Collection(s)
- Ciències de la Salut [712]
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/