Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance

• DOI: 10.1016/j.cmet.2017.06.014
• Publication Date: 2017-07-05T16:49:09Z
• Authors: Noelia Martínez-S...; Patricia Seoane-C...; Cristina Contreras; Luis Varela; Joan Villarroya; Eva Rial-Pensado; Xabier Buqué; Igor Aurrekoetxea; Teresa C. Delgado; Rafael Vázquez-Ma...; Ismael González-G...; Juan Roa; Andrew J. Whittle; Beatriz Gomez-Santos; Vidya Velagapudi; Y.C. Loraine Tung; Donald A. Morgan; Peter J. Voshol; Pablo B. Martínez...; Tania López-González; Laura Liñares-Pose; Francisco Gonzalez; Krishna Chatterjee; Tomás Sobrino; Gema Medina-Gómez; Roger J. Davis; Núria Casals; Matej Orešič; Anthony P. Coll; Antonio Vidal-Puig; Jens Mittag; Manuel Tena-Sempere; María M. Malagón; Carlos Diéguez; María Luz Martíne...; Patricia Aspichueta; Kamal Rahmouni; Rubén Nogueiras; Guadalupe Sabio; Francesc Villarroya; Miguel López
• Keywords: Lipogenesis

Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis liver and lipid oxidation brown adipose tissue (BAT) through parasympathetic (PSNS) sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic with parallel stimulation of thermogenic program BAT. The action depends on AMP-activated protein kinase (AMPK)-induced regulation two signaling pathways ventromedial nucleus hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which BAT thermogenesis, increased c-Jun N-terminal (JNK) activation, controls metabolism. Of note, ablation AMPKα1 steroidogenic factor 1 (SF1) neurons VMH fully recapitulated effect T3, pointing this population mediating THs Overall, these findings uncover underlying modulates peripheral