Hypothalamic AMPK-ER Stress-JNK1 axis mediates the central actions of thyroid hormones on energy balance
| العنوان: | Hypothalamic AMPK-ER Stress-JNK1 axis mediates the central actions of thyroid hormones on energy balance |
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| المؤلفون: | Juan Carlos Roa, Luis M. Varela, Patricia Seoane-Collazo, Tomás Sobrino, Eva Rial-Pensado, Miguel López, Roger J. Davis, Vidya Velagapudi, Andrew J. Whittle, Pablo B. Martínez de Morentin, Gema Medina-Gómez, Carlos Dieguez, Rubén Nogueiras, Kamal Rahmouni, Laura Liñares-Pose, Antonio Vidal-Puig, Rafael Vázquez-Martínez, Teresa C. Delgado, Ismael González-García, Matej Orešič, Guadalupe Sabio, Cristina Contreras, Y. C. Loraine Tung, Xabier Buqué, Patricia Aspichueta, Igor Aurrekoetxea, Beatriz Gomez-Santos, Francesc Villarroya, Núria Casals, Noelia Martínez-Sánchez, Donald A. Morgan, Manuel Tena-Sempere, Anthony P. Coll, María L. Martínez-Chantar, Peter J. Voshol, Tania López-González, Joan Villarroya, María M. Malagón, Francisco Gonzalez, Jens Mittag, Krishna Chatterjee |
| المساهمون: | University of Helsinki, Institute for Molecular Medicine Finland, Chatterjee, Krishna [0000-0002-2654-8854], Coll, Anthony [0000-0003-2594-7463], Vidal-Puig, Antonio [0000-0003-4220-9577], Apollo - University of Cambridge Repository, Unión Europea. Comisión Europea, Xunta de Galicia (España), Regional Government of Andalusia (España), Basque Government (España), EITB - Radio Televisión Pública Vasca, Instituto de Salud Carlos III, Government of Catalonia (España), Fundación La Marató TV3, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Ministerio de Economía y Competitividad (España), Asociación Española Contra el Cáncer, Medical Research Council (Reino Unido), Wellcome Trust, Deutsche Forschungsgemeinschaft (Alemania), National Institutes of Health (Estados Unidos), American Heart Association, Fraternal Order of Eagles (Estados Unidos), European Foundation for the Study of Diabetes, Fundación AstraZeneca, Atresmedia, Fundación ProCNIC, University of Iowa (Estados Unidos) |
| المصدر: | Cell Metabolism CELL METABOLISM r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu Fundació Sant Joan de Déu Martínez-Sánchez, N, Seoane-Collazo, P, Contreras, C, Varela, L, Villarroya, J, Rial-Pensado, E, Buqué, X, Aurrekoetxea, I, Delgado, T C, Vázquez-Martínez, R, González-García, I, Roa, J, Whittle, A J, Gomez-Santos, B, Velagapudi, V, Tung, Y C L, Morgan, D A, Voshol, P J, Martínez de Morentin, P B, López-González, T, Liñares-Pose, L, Gonzalez, F, Chatterjee, K, Sobrino, T, Medina-Gómez, G, Davis, R J, Casals, N, Orešič, M, Coll, A P, Vidal-Puig, A, Mittag, J, Tena-Sempere, M, Malagón, M M, Diéguez, C, Martínez-Chantar, M L, Aspichueta, P, Rahmouni, K, Nogueiras, R, Sabio, G, Villarroya, F & López, M 2017, ' Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance ', Cell Metabolism, vol. 26, no. 1, pp. 212-229.e12 . https://doi.org/10.1016/j.cmet.2017.06.014Test Recercat: Dipósit de la Recerca de Catalunya Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid Repisalud Instituto de Salud Carlos III (ISCIII) Recercat. Dipósit de la Recerca de Catalunya instname r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu |
| بيانات النشر: | Elsevier, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, AMPK, Male, HOMEOSTASIS, Adipose Tissue, Brown/metabolism, Physiology, Obesidad, Neurones, AMPK, BAT, ER stress, JNK1, SF1, VMH, autonomic nervous system, ceramides, liver, thyroid hormones, Inbred C57BL, Neuronas, Rats, Sprague-Dawley, Mice, 0302 clinical medicine, Adipose Tissue, Brown, Brown adipose tissue, NEURONS, Mitogen-Activated Protein Kinase 8/metabolism, Metabolismo, Neurons, INSULIN-RESISTANCE, Triiodothyronine, Thermogenesis, Metabolisme, SF1, medicine.anatomical_structure, Thyroid Hormones/metabolism, Lipogenesis, Obesitat, ER stress, Signal Transduction, Liver/metabolism, ADIPOSE-TISSUE THERMOGENESIS, medicine.medical_specialty, DIET-INDUCED OBESITY, Tejido adiposo, Hypothalamus, RAT-LIVER, Adipose tissue, Biology, METABOLISM, liver, Resistencia a la insulina, Article, 03 medical and health sciences, Lipid oxidation, BROWN FAT, Brown/metabolism, Internal medicine, medicine, Animals, Mitogen-Activated Protein Kinase 8, Obesity, Molecular Biology, VLDL SECRETION, thyroid hormones, Insulinoresistència, ceramides, Hypothalamus/metabolism, RECEPTOR, autonomic nervous system, ta1182, JNK1, BAT, Lipid metabolism, Insulin resistance, Cell Biology, Triiodothyronine/metabolism, VMH, Lipid Metabolism, Rats, Mice, Inbred C57BL, Teixit adipós, 030104 developmental biology, Endocrinology, Metabolism, Unfolded protein response, 1182 Biochemistry, cell and molecular biology, Sprague-Dawley, 3111 Biomedicine, Energy Metabolism, 030217 neurology & neurosurgery |
| الوصف: | Summary 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. Graphical Abstract Highlights • Central T3 regulates lipogenesis in liver via the parasympathetic nervous system • Central T3 regulates lipid oxidation in BAT via the sympathetic nervous system • Ablation of AMPK in SF1 neurons of the VMH recapitulates the effects of T3 • Hypothalamic JNK1 and ceramides/ER stress mediate T3 actions on liver and BAT 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1550-4131 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e733f585dace6e40c0df186f7c9cd8cTest http://hdl.handle.net/20.500.12328/1546Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0e733f585dace6e40c0df186f7c9cd8c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15504131 |
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