ArticleCell metabolism2017
Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance.
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Article in Cell metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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130citing papers in PubMed
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130 citing papers in PubMed, 211 citations in OpenAlex.
- Endocrine-Metabolic Crosstalk Between Diabetes Mellitus and Hypothyroidism: From Network Mechanisms to Translational Stratification.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
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- POMC AMPKα1 deletion drives male-specific BAT thermogenesis and obesity resistance.EMBO reports · 2026Article
- Functional genomic dissection and prediction of body size traits in pigs.Genetics, selection, evolution : GSE · 2026Article
- Hypothalamic Control of Liver Health and Disease: From Circuits to Pathophysiology and Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Synergistic Intervention for Obesity: Integrating Central Appetite Regulation and Peripheral Energy Expenditure.Current obesity reports · 2026Review
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- Hypothalamic regulation of energy homeostasis: Quo vadis.Reviews in endocrine & metabolic disorders · 2026Review
- Hypothalamic actions of estrogens in the regulation of energy and glucose homeostasis.Reviews in endocrine & metabolic disorders · 2026Review
- From diet to hypothalamic dysfunction: Neuroanatomical and hormonal integration of the microbiota-hypothalamus-adipose tissue axis.Reviews in endocrine & metabolic disorders · 2026Review
- Body weight and waist circumference are differentially associated with the response to L-thyroxine treatment in primary hypothyroidism.Journal of clinical & translational endocrinology · 2026Article
- Revitalizing p-GSK-3β via cysteine sulfenylation promotes hepatic insulin resistance by differentially regulating glycogenesis and gluconeogenesis.Nature metabolism · 2026Article
- Attack of the kinases: JNK signaling in metabolism.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Review
- Hypothalamic endoplasmic reticulum stress drives pubertal precocity due to early-onset obesity in female rodents.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- NAFLD and Hypothyroidism: Deciphering Pivotal Genetic Variants, Cellular Expression Landscapes, and Spatial Architectures.International journal of molecular sciences · 2026Article
- Relationship Between Body Composition and Quality of Life in Young Patients With Differentiated Thyroid Carcinoma After Thyroidectomy.International journal of endocrinology · 2026Article
- Low-normal free thyroxine is associated with a higher prevalence of lower extremity arterial disease in euthyroid type 2 diabetes mellitus.Scientific reports · 2025Article
- Effects of Saccharomyces cerevisiae on Pancreatic Alpha and Beta Cells and Metabolic Profile in Broilers.Probiotics and antimicrobial proteins · 2025Article
- Thyroid Response to Peripheral Endocrine Factors: Neuropeptide Y Influences Thyroid Function in the ReptileInternational journal of molecular sciences · 2025Article
70 more citing papers are in PubMed but not listed here.
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Authors and funding
41 authors at 20 institutions in 5 countries.
Noelia Martínez-SánchezDepartment of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain.
Patricia Seoane-CollazoDepartment of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain.
Cristina ContrerasDepartment of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain.
Luis VarelaDepartment of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain.
Joan VillarroyaCIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain; Departament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina, Universitat de Barcelona (IBUB), Barcelona 08028, Spain; Hospital de la Santa Creu i Sant Pau, Barcelona 08026, Spain.
Eva Rial-PensadoDepartment of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain.
Xabier BuquéDepartment of Physiology, University of the Basque Country UPV/EHU, Biocruces Research Institute, Barakaldo 48903, Spain.
Igor AurrekoetxeaDepartment of Physiology, University of the Basque Country UPV/EHU, Biocruces Research Institute, Barakaldo 48903, Spain.
Teresa C DelgadoCIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Technology Park of Bizkaia, Derio, Bizkaia 48160, Spain.
Rafael Vázquez-MartínezCIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Universitario Reina Sofía, Córdoba 14004, Spain.
Ismael González-GarcíaDepartment of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain.
Juan RoaCIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Universitario Reina Sofía, Córdoba 14004, Spain.
Andrew J WhittleUniversity of Cambridge Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
Beatriz Gomez-SantosDepartment of Physiology, University of the Basque Country UPV/EHU, Biocruces Research Institute, Barakaldo 48903, Spain.
Vidya VelagapudiVTT Technical Research Centre of Finland, Tietotie 2, Espoo FIN-02044, Finland; Metabolomics Unit, Institute for Molecular Medicine, University of Helsinki, Helsinki FI-00290, Finland.
Y C Loraine TungUniversity of Cambridge Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
Donald A MorganDepartment of Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
Peter J VosholUniversity of Cambridge Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
Pablo B Martínez de MorentinDepartment of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain.
Tania López-GonzálezDepartment of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain; Clinical Neurosciences Research Laboratory, Department of Neurology, Hospital Clínico Universitario, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain.
Laura Liñares-PoseDepartment of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain.
Francisco GonzalezDepartment of Surgery, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; Service of Ophthalmology, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela 15706, Spain.
Krishna ChatterjeeUniversity of Cambridge Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
Tomás SobrinoClinical Neurosciences Research Laboratory, Department of Neurology, Hospital Clínico Universitario, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain.
Gema Medina-GómezUniversity Rey Juan Carlos, Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Avda. de Atenas s/n, Alcorcon, Madrid 28922, Spain.
Roger J DavisProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Howard Hughes Medical Institute, Worcester, MA 01605, USA.
Núria CasalsCIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain; Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Sant Cugat del Vallés, Barcelona 08195, Spain.
Matej OrešičTurku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku FI-20520, Finland.
Anthony P CollUniversity of Cambridge Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
Antonio Vidal-PuigUniversity of Cambridge Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
Jens MittagUniversity of Lübeck, Internal Medicine I, Center of Brain, Behavior, and Metabolism (CBBM), Ratzeburger Allee 160, Lübeck 23562, Germany.
Manuel Tena-SempereCIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Universitario Reina Sofía, Córdoba 14004, Spain; FiDiPro Program, Department of Physiology, University of Turku, Kiinamyllynkatu 10, Turku FIN-20520, Finland.
María M MalagónCIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Universitario Reina Sofía, Córdoba 14004, Spain.
Carlos DiéguezDepartment of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain.
María Luz Martínez-ChantarCIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Technology Park of Bizkaia, Derio, Bizkaia 48160, Spain.
Patricia AspichuetaDepartment of Physiology, University of the Basque Country UPV/EHU, Biocruces Research Institute, Barakaldo 48903, Spain.
Kamal RahmouniDepartment of Pharmacology, University of Iowa, Iowa City, IA 52242, USA; Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
Rubén NogueirasDepartment of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain.
Guadalupe SabioMyocardial Pathophysiology, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
Francesc VillarroyaCIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain; Departament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina, Universitat de Barcelona (IBUB), Barcelona 08028, Spain.
Miguel LópezDepartment of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain. Electronic address: m.lopez@usc.es.
Instituto de Investigación Sanitaria de Santiago · ESUniversidade de Santiago de Compostela · ESCenter for Research in Molecular Medicine and Chronic Diseases · ESWellcome/MRC Institute of Metabolic Science · GBBioCruces Health research Institute · ESCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · ESHospital Universitario Reina Sofía · ESUniversitat de Barcelona · ESUniversity of Cambridge · GBUniversity of Iowa · USUniversity of the Basque Country · ESCentro de Investigación Biomédica en Red · ESComplejo Hospitalario Universitario de Santiago · ESHoward Hughes Medical Institute · USSpanish National Centre for Cardiovascular Research · ESTieto (Finland) · FIUniversidad Rey Juan Carlos · ESUniversitat Internacional de Catalunya · ESUniversity of Córdoba · ESUniversity of Lübeck · DE
Funding
Role of the brain Renin-Angiotensin Sys. in Cardiovas and Metabolic RegulationP01HL084207 · NHLBI · UNIVERSITY OF IOWA · PI GROBE, JUSTIN L · 2007 to 2022
$30.2MAdipose Tissue Metabolic Stress ResponsesR01DK112698 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI DAVIS, ROGER J. · 2017 to 2025
$4.4MMetabolic Stress SignalingR01DK107220 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI DAVIS, ROGER J. · 2016 to 2023
$3.6MMedical Research Council G9824984Medical Research Council MC_UU_12012/1Medical Research Council MC_UU_12012/2Medical Research Council MC_UU_12012/5Medical Research Council MC_UU_12015/5NHLBI NIH HHS P01 HL084207NIDDK NIH HHS R01 DK107220NIDDK NIH HHS R01 DK112698Wellcome Trust
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.
Indexed as
Energy MetabolismSignal TransductionAdipose Tissue, BrownAnimalsHypothalamusLipid MetabolismLiverMaleMice, Inbred C57BLMitogen-Activated Protein Kinase 8RatsRats, Sprague-DawleyThermogenesisThyroid HormonesTriiodothyronineMitogen-Activated Protein Kinase 8Thyroid HormonesTriiodothyronineAMPKautonomic nervous systemBATceramidesER stressJNK1liverSF1thyroid hormonesVMH
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