JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism
Objective: Hypothalamic energy sensors, such as AMP-activated protein kinase (AMPK), and stress sensors, such as c-Jun N-terminal kinase 1 (JNK1, also known as MAPK8) modulate whole body energy balance. While the role of AMPK in steroidogenic factor 1 (SF1) neurons of the VMH has been investigated,...
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Elsevier
2025-08-01
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| Series: | Molecular Metabolism |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877825000778 |
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| author | Iara Fernández-González Oscar Freire-Agulleiro Vitor Ferreira María Silveira-Loureiro Eva Rial-Pensado Pablo Garrido-Gil Gloria Martínez Patricia Rada José L. Labandeira-García Jens Mittag Ismael González-García Carlos Diéguez Rubén Nogueiras Ángela M. Valverde Roger J. Davis Guadalupe Sabio Olga Barca-Mayo Miguel López |
| author_facet | Iara Fernández-González Oscar Freire-Agulleiro Vitor Ferreira María Silveira-Loureiro Eva Rial-Pensado Pablo Garrido-Gil Gloria Martínez Patricia Rada José L. Labandeira-García Jens Mittag Ismael González-García Carlos Diéguez Rubén Nogueiras Ángela M. Valverde Roger J. Davis Guadalupe Sabio Olga Barca-Mayo Miguel López |
| author_sort | Iara Fernández-González |
| collection | DOAJ |
| description | Objective: Hypothalamic energy sensors, such as AMP-activated protein kinase (AMPK), and stress sensors, such as c-Jun N-terminal kinase 1 (JNK1, also known as MAPK8) modulate whole body energy balance. While the role of AMPK in steroidogenic factor 1 (SF1) neurons of the VMH has been investigated, the relevance of JNK1 in this neuronal population has not been addressed. Here, we investigated the involvement of JNK1 SF1 on energy homeostasis. Methods: We generated mice bearing conditional JNK1 disruption through Mapk8 gene deletion in SF1 neurons (Sf1Cre/Jnk1fl/fl). Complete metabolic phenotyping, fasting/refeeding and cold challenges, as well as the central response to triiodothyronine (T3) on brown adipose tissue (BAT) thermogenesis and hepatic lipid metabolism were carried out. Results: Sf1Cre/Jnk1fl/fl mice displayed decreased body weight, improved glucose tolerance, and reduced hepatic lipid levels. However, Sf1Cre/Jnk1fl/fl did not properly defend their temperature upon cold exposure. While central administration of T3 elicited feeding independent weight loss in both wildtype (Jnk1fl/fl) and SF1Cre/Jnk1fl/fl mice, it did not promote hepatic lipid accretion in null animals. Conclusions: Our data demonstrated for the first time that JNK1 in SF1 neurons is necessary for the regulation of hepatic lipid metabolism, cold adaptation and central T3 actions. |
| format | Article |
| id | doaj-art-485939e7a2b2464092af8fd5793edcee |
| institution | Kabale University |
| issn | 2212-8778 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj-art-485939e7a2b2464092af8fd5793edcee2025-08-20T03:28:14ZengElsevierMolecular Metabolism2212-87782025-08-019810217010.1016/j.molmet.2025.102170JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolismIara Fernández-González0Oscar Freire-Agulleiro1Vitor Ferreira2María Silveira-Loureiro3Eva Rial-Pensado4Pablo Garrido-Gil5Gloria Martínez6Patricia Rada7José L. Labandeira-García8Jens Mittag9Ismael González-García10Carlos Diéguez11Rubén Nogueiras12Ángela M. Valverde13Roger J. Davis14Guadalupe Sabio15Olga Barca-Mayo16Miguel López17Department of Physiology, CiMUS, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Santiago de Compostela, SpainDepartment of Physiology, CiMUS, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Santiago de Compostela, SpainDepartment of Physiology, CiMUS, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain; Instituto de Investigaciones Biomedicas Sols-Morreale (IIBM), CSIC-UAM, 28029, Madrid, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, 28029, Madrid, SpainDepartment of Physiology, CiMUS, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Santiago de Compostela, SpainDepartment of Physiology, CiMUS, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Santiago de Compostela, SpainDepartment of Morphological Sciences, CiMUS, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain; CIBER Enfermedades Neurodegenerativas (CIBERNED), 15782, Santiago de Compostela, SpainCenter for Experimental Biomedicine (CEBEGA), University of Santiago de Compostela, 15782, Santiago de Compostela, SpainInstituto de Investigaciones Biomedicas Sols-Morreale (IIBM), CSIC-UAM, 28029, Madrid, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, 28029, Madrid, SpainDepartment of Morphological Sciences, CiMUS, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain; CIBER Enfermedades Neurodegenerativas (CIBERNED), 15782, Santiago de Compostela, SpainInstitute for Experimental Endocrinology, Center of Brain Behavior & Metabolism, University of Lübeck, 23562, Lübeck, GermanyDepartment of Physiology, CiMUS, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Santiago de Compostela, SpainDepartment of Physiology, CiMUS, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Santiago de Compostela, SpainDepartment of Physiology, CiMUS, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Santiago de Compostela, SpainInstituto de Investigaciones Biomedicas Sols-Morreale (IIBM), CSIC-UAM, 28029, Madrid, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, 28029, Madrid, SpainProgram in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USACentro Nacional de Investigaciones Oncológicas (CNIO), 28029, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029, Madrid, SpainDepartment of Physiology, CiMUS, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain; Corresponding author. Department of Physiology, CiMUS, University of Santiago de Compostela, 15782, Santiago de Compostela, SpainDepartment of Physiology, CiMUS, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Santiago de Compostela, Spain; Corresponding author. Department of Physiology, CiMUS, University of Santiago de Compostela, 15782, Santiago de Compostela, SpainObjective: Hypothalamic energy sensors, such as AMP-activated protein kinase (AMPK), and stress sensors, such as c-Jun N-terminal kinase 1 (JNK1, also known as MAPK8) modulate whole body energy balance. While the role of AMPK in steroidogenic factor 1 (SF1) neurons of the VMH has been investigated, the relevance of JNK1 in this neuronal population has not been addressed. Here, we investigated the involvement of JNK1 SF1 on energy homeostasis. Methods: We generated mice bearing conditional JNK1 disruption through Mapk8 gene deletion in SF1 neurons (Sf1Cre/Jnk1fl/fl). Complete metabolic phenotyping, fasting/refeeding and cold challenges, as well as the central response to triiodothyronine (T3) on brown adipose tissue (BAT) thermogenesis and hepatic lipid metabolism were carried out. Results: Sf1Cre/Jnk1fl/fl mice displayed decreased body weight, improved glucose tolerance, and reduced hepatic lipid levels. However, Sf1Cre/Jnk1fl/fl did not properly defend their temperature upon cold exposure. While central administration of T3 elicited feeding independent weight loss in both wildtype (Jnk1fl/fl) and SF1Cre/Jnk1fl/fl mice, it did not promote hepatic lipid accretion in null animals. Conclusions: Our data demonstrated for the first time that JNK1 in SF1 neurons is necessary for the regulation of hepatic lipid metabolism, cold adaptation and central T3 actions.http://www.sciencedirect.com/science/article/pii/S2212877825000778HypothalamusSF1JNK1BATLiverT3 |
| spellingShingle | Iara Fernández-González Oscar Freire-Agulleiro Vitor Ferreira María Silveira-Loureiro Eva Rial-Pensado Pablo Garrido-Gil Gloria Martínez Patricia Rada José L. Labandeira-García Jens Mittag Ismael González-García Carlos Diéguez Rubén Nogueiras Ángela M. Valverde Roger J. Davis Guadalupe Sabio Olga Barca-Mayo Miguel López JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism Molecular Metabolism Hypothalamus SF1 JNK1 BAT Liver T3 |
| title | JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism |
| title_full | JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism |
| title_fullStr | JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism |
| title_full_unstemmed | JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism |
| title_short | JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism |
| title_sort | jnk1 in sf1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism |
| topic | Hypothalamus SF1 JNK1 BAT Liver T3 |
| url | http://www.sciencedirect.com/science/article/pii/S2212877825000778 |
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