TY - JOUR
T1 - Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance
AU - Martínez-Sánchez, Noelia
AU - Seoane-Collazo, Patricia
AU - Contreras, Cristina
AU - Varela, Luis
AU - Villarroya, Joan
AU - Rial-Pensado, Eva
AU - Buqué, Xabier
AU - Aurrekoetxea, Igor
AU - Delgado, Teresa C.
AU - Vázquez-Martínez, Rafael
AU - González-García, Ismael
AU - Roa, Juan
AU - Whittle, Andrew J.
AU - Gomez-Santos, Beatriz
AU - Velagapudi, Vidya
AU - Tung, Y.C. Loraine
AU - Morgan, Donald A.
AU - Voshol, Peter J.
AU - Martínez de Morentin, Pablo B.
AU - López-González, Tania
AU - Liñares-Pose, Laura
AU - Gonzalez, Francisco
AU - Chatterjee, Krishna
AU - Sobrino, Tomás
AU - Medina-Gómez, Gema
AU - Davis, Roger J.
AU - Casals, Núria
AU - Orešič, Matej
AU - Coll, Anthony P.
AU - Vidal-Puig, Antonio
AU - Mittag, Jens
AU - Tena-Sempere, Manuel
AU - Malagón, María M.
AU - Diéguez, Carlos
AU - Martínez-Chantar, María Luz
AU - Aspichueta, Patricia
AU - Rahmouni, Kamal
AU - Nogueiras, Rubén
AU - Sabio, Guadalupe
AU - Villarroya, Francesc
AU - López, Miguel
N1 - Open Access funded by European Research Council
PY - 2017/7/5
Y1 - 2017/7/5
N2 - 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.
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.
KW - thyroid hormones
KW - VMH
KW - SF1
KW - AMPK
KW - ceramides
KW - ER stress
KW - JNK1
KW - autonomic nervous system
KW - liver
KW - BAT
U2 - 10.1016/j.cmet.2017.06.014
DO - 10.1016/j.cmet.2017.06.014
M3 - Article
SN - 1550-4131
VL - 26
SP - 212
EP - 229
JO - Cell Metabolism
JF - Cell Metabolism
IS - 1
ER -