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Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance
Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain.
Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesid.
Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain .
Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain.
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2017 (English)In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 26, no 1, 212-229.e12 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Cambridge, MA, United States: Cell Press , 2017. Vol. 26, no 1, 212-229.e12 p.
Keyword [en]
AMPK, BAT, ER stress, JNK1, SF1, VMH, autonomic nervous system, ceramides, liver, thyroid hormones
National Category
Medical and Health Sciences Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:oru:diva-59392DOI: 10.1016/j.cmet.2017.06.014ISI: 000404885800023PubMedID: 28683288OAI: oai:DiVA.org:oru-59392DiVA: diva2:1136180
Funder
Wellcome trust, 095564/Z/11/ZNIH (National Institute of Health), DK107220, DK112698, HL084207Eli Lilly, GIM/EFS1601AstraZeneca
Note

Funding Agencies:

European Community, Projektnr. 260464, 281854

Xunta de Galicia, Projektnr. ED431C-2016-025, ED341D-R2016-032, 2015-CP080,  2016-PG057, 2015-CP079, 2016-PG068, ED481A-2016/094, 2016-2019,  ED431G/05 

Junta de Andalucia, Projektnr. P12-FQM-01943

Gobierno Vasco-Departamento de Salud, Projektnr. 2013111114

EITB, Projektnr. BIO15/CA/014

Ayudas para apoyar grupos de investigacion del sistema Universitario Vasco, Projektnr. IT971-16

Generalitat de Catalunya, Projektnr. 2014SGR465

Fundacio La Marato de TV3, Projektnr. 87/C/2016

Instituto de Salud Carlos III - FEDER, Projektnr. RD16/0008/ 0003, PIE14/00031

Ministerio de Economia y Competitividad (MINECO) - FEDER Program of EU, Projektnr. SAF2014-52223-C2-2-R, BFU2014-57581-P -P, BFU2013-44229-R, BFU2014-55871-P, SAF2014-54658-R, SAF2015-64352-R, BFU2015-70664R, SAF2013-43506-R, SAF2014 55725, SAF2015-71026-R, BFU2015-70454-REDT/Adipoplast  

Asociacion Espanola contra el Cancer

Medical Research Council (MRC) Metabolic Diseases Unit, Projektnr. MRC_MC_UU_12012/1, MRC_UU_12015/5 

MRC Programme Grant, Projektnr. G9824984

MRC Disease Model Core

Deutsche Forschungsgemeinschaft, Projektnr. Mi1242/2-1

American Heart Association (EIA), Projektnr. 14EIA18860041

University of Iowa Fraternal Order of Eagles Diabetes Research Center

European Foundation for the Study of Diabetes

Atresmedia Corporacion

ISCIII , Projektnr. CD14/0007, CP12/03121

MINECO, Projektnr. IJDC-2014-19681, BES-2015-072743, FPU12/01827, SEV-2015-0505

AECC, Projektnr. AIO2013

Pro-CNIC Foundation

Available from: 2017-08-25 Created: 2017-08-25 Last updated: 2017-09-25Bibliographically approved

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Oresic, Matej

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