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 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. Martínez-Sánchez et al. show that thyroid hormones act in the hypothalamus to regulate hepatic lipogenesis and brown fat lipid oxidation via the parasympathetic and sympathetic nervous systems. These peripheral effects are orchestrated by two distinct signaling pathways in the VMH, JNK1 and ceramides/ER stress, which are under AMPK control.
| Original language | English |
|---|---|
| Pages (from-to) | 212-229.e12 |
| Journal | Cell Metabolism |
| Volume | 26 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 5 Jul 2017 |
| MoE publication type | A1 Journal article-refereed |
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Keywords
- AMPK
- BAT
- ER stress
- JNK1
- SF1
- VMH
- Male
- Thyroid Hormones/metabolism
- Liver/metabolism
- Adipose Tissue, Brown/metabolism
- Mitogen-Activated Protein Kinase 8/metabolism
- Triiodothyronine/metabolism
- Signal Transduction
- Mice, Inbred C57BL
- Rats
- Lipid Metabolism
- Rats, Sprague-Dawley
- Hypothalamus/metabolism
- Animals
- Thermogenesis
- Energy Metabolism
Cite this
}
Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance. / Martínez-Sánchez, Noelia; Seoane-Collazo, Patricia; Contreras, Cristina; Varela, Luis; Villarroya, Joan; Rial-Pensado, Eva; Buqué, Xabier; Aurrekoetxea, Igor; Delgado, Teresa C.; Vázquez-Martínez, Rafael; González-García, Ismael; Roa, Juan; Whittle, Andrew J.; Gomez-Santos, Beatriz; Velagapudi, Vidya; Tung, Y. C.Loraine; Morgan, Donald A.; Voshol, Peter J.; Martínez de Morentin, Pablo B.; López-González, Tania; Liñares-Pose, Laura; Gonzalez, Francisco; Chatterjee, Krishna; Sobrino, Tomás; Medina-Gómez, Gema; Davis, Roger J.; Casals, Núria; Orešič, Matej; Coll, Anthony P.; Vidal-Puig, Antonio; Mittag, Jens; Tena-Sempere, Manuel; Malagón, María M.; Diéguez, Carlos; Martínez-Chantar, María Luz; Aspichueta, Patricia; Rahmouni, Kamal; Nogueiras, Rubén; Sabio, Guadalupe; Villarroya, Francesc; López, Miguel.
In: Cell Metabolism, Vol. 26, No. 1, 05.07.2017, p. 212-229.e12.Research output: Contribution to journal › Article › Scientific › peer-review
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
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. Martínez-Sánchez et al. show that thyroid hormones act in the hypothalamus to regulate hepatic lipogenesis and brown fat lipid oxidation via the parasympathetic and sympathetic nervous systems. These peripheral effects are orchestrated by two distinct signaling pathways in the VMH, JNK1 and ceramides/ER stress, which are under AMPK control.
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. Martínez-Sánchez et al. show that thyroid hormones act in the hypothalamus to regulate hepatic lipogenesis and brown fat lipid oxidation via the parasympathetic and sympathetic nervous systems. These peripheral effects are orchestrated by two distinct signaling pathways in the VMH, JNK1 and ceramides/ER stress, which are under AMPK control.
KW - AMPK
KW - BAT
KW - ER stress
KW - JNK1
KW - SF1
KW - VMH
KW - Male
KW - Thyroid Hormones/metabolism
KW - Liver/metabolism
KW - Adipose Tissue, Brown/metabolism
KW - Mitogen-Activated Protein Kinase 8/metabolism
KW - Triiodothyronine/metabolism
KW - Signal Transduction
KW - Mice, Inbred C57BL
KW - Rats
KW - Lipid Metabolism
KW - Rats, Sprague-Dawley
KW - Hypothalamus/metabolism
KW - Animals
KW - Thermogenesis
KW - Energy Metabolism
UR - http://www.scopus.com/inward/record.url?scp=85032692524&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2017.06.014
DO - 10.1016/j.cmet.2017.06.014
M3 - Article
AN - SCOPUS:85032692524
VL - 26
SP - 212-229.e12
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 1
ER -