Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/6501
Title
Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance
Author(s)
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, Nuria | 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, Ruben | Sabio, Guadalupe CNIC | Villarroya, Francesc | Lopez, Miguel
Date issued
2017
Citation
Cell Metab. 2017; 26(1):212-229 e12
Language
Inglés
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.
Subject
DIET-INDUCED OBESITY | ADIPOSE-TISSUE THERMOGENESIS | RAT-LIVER | INSULIN-RESISTANCE | VLDL SECRETION | BROWN FAT | NEURONS | METABOLISM | RECEPTOR | HOMEOSTASIS
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