Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance
Casals N; Aspichueta P; Villarroya F; de Morentin PBM; Coll AP; Oresic M; Roa J; Sobrino T; Lopez-Gonzalez T; Rahmouni K; Medina-Gómez G; Buqué X; Morgan DA; Villarroya J; Aurrekoetxea I; Seoane-Collazo P; Varela L; Gomez-Santos B; González-García I; Mittag J; Malagón MM; Davis RJ; Martinez-Chantar ML; Gonzalez F; Liñares-Pose L; López M; Contreras C; Vidal-Puig A; Rial-Pensado E; Nogueiras R; Velagapudi V; Whittle AJ; Vazquez-Martinez R; Tung YCL; Martinez-Sánchez N; Tena-Sempere M; Diéguez C; Voshol PJ; Sabio G; Chatterjee K; Delgado TC
Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance
Casals N
Aspichueta P
Villarroya F
de Morentin PBM
Coll AP
Oresic M
Roa J
Sobrino T
Lopez-Gonzalez T
Rahmouni K
Medina-Gómez G
Buqué X
Morgan DA
Villarroya J
Aurrekoetxea I
Seoane-Collazo P
Varela L
Gomez-Santos B
González-García I
Mittag J
Malagón MM
Davis RJ
Martinez-Chantar ML
Gonzalez F
Liñares-Pose L
López M
Contreras C
Vidal-Puig A
Rial-Pensado E
Nogueiras R
Velagapudi V
Whittle AJ
Vazquez-Martinez R
Tung YCL
Martinez-Sánchez N
Tena-Sempere M
Diéguez C
Voshol PJ
Sabio G
Chatterjee K
Delgado TC
CELL PRESS
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042716980
https://urn.fi/URN:NBN:fi-fe2021042716980
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]