期刊
CELL METABOLISM
卷 26, 期 1, 页码 212-+出版社
CELL PRESS
DOI: 10.1016/j.cmet.2017.06.014
关键词
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资金
- European Community [260464, 281854]
- Xunta de Galicia [ED431C-2016-025, ED341D-R2016-032, 2015-CP080, 2016-PG057, 2015-CP079, 2016-PG068, ED481A-2016/094, 2016-2019, ED431G/05]
- Junta de Andalucia [P12-FQM-01943]
- Gobierno Vasco-Departamento de Salud [2013111114]
- EITB [BIO15/CA/014]
- Ayudas para apoyar grupos de investigacion del sistema Universitario Vasco [IT971-16]
- Generalitat de Catalunya [2014SGR465]
- Fundacio La Marato de TV3 [87/C/2016]
- Instituto de Salud Carlos III - FEDER [RD16/0008/ 0003, PIE14/00031]
- Ministerio de Economia y Competitividad (MINECO) - FEDER Program of EU [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 [MRC_MC_UU_12012/1, MRC_UU_12015/5]
- MRC Programme Grant [G9824984]
- MRC Disease Model Core
- Wellcome Trust Investigator Award [095564/Z/11/Z]
- Deutsche Forschungsgemeinschaft [Mi1242/2-1]
- NIH [DK107220, DK112698, HL084207]
- American Heart Association (EIA) [14EIA18860041]
- University of Iowa Fraternal Order of Eagles Diabetes Research Center
- EFSD/Lilly Programme [GIM/EFS1601]
- Astra Zeneca Foundation
- European Foundation for the Study of Diabetes
- Atresmedia Corporacion
- ISCIII [CD14/0007, CP12/03121]
- MINECO [IJDC-2014-19681, BES-2015-072743, FPU12/01827, SEV-2015-0505]
- AECC [AIO2013]
- Pro-CNIC Foundation
- European Research Council (ERC) [260464] Funding Source: European Research Council (ERC)
- Wellcome Trust [095564/Z/11/Z] Funding Source: Wellcome Trust
- Medical Research Council [MC_UU_12012/2, MC_UU_12012/5, MC_UU_12012/5/B] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0514-10176] Funding Source: researchfish
- MRC [MC_UU_12012/1, MC_UU_12012/5, MC_UU_12012/2, G9824984] Funding Source: UKRI
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.
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