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dc.contributor.authorSeoane Collazo, Patricia
dc.contributor.authorRial Pensado, Eva
dc.contributor.authorEstévez Salguero, Ánxela María
dc.contributor.authorMilbank, Edward
dc.contributor.authorGarcía Caballero, Lucía
dc.contributor.authorRíos García, Marcos
dc.contributor.authorLiñares Pose, Laura
dc.contributor.authorScotece, Morena
dc.contributor.authorGallego Gómez, María Rosalía
dc.contributor.authorFernández-Real, Jose Manuel
dc.contributor.authorNogueiras Pozo, Rubén
dc.contributor.authorDiéguez González, Carlos
dc.contributor.authorGualillo, Oreste
dc.contributor.authorLópez Pérez, Miguel Antonio
dc.date.accessioned2022-08-24T11:49:10Z
dc.date.available2022-08-24T11:49:10Z
dc.date.issued2021
dc.identifier.citationArthritis & Rheumatology 74, 2, 2022, 212–222. https://doi.org/10.1002/art.41950
dc.identifier.urihttp://hdl.handle.net/10347/29137
dc.description.abstractObjective: To investigate whether thermogenesis and the hypothalamus may be involved in the physiopathology of experimental arthritis (EA). Methods: EA was induced in male Lewis rats by intradermal injection of Freund's complete adjuvant (CFA). Food intake, body weight, plasma cytokines, thermographic analysis, gene and protein expression of thermogenic markers in brown adipose tissue (BAT) and white adipose tissue (WAT), and hypothalamic AMP-activated protein kinase (AMPK) were analyzed. Virogenetic activation of hypothalamic AMPK was performed. Results: We first demonstrated that EA was associated with increased BAT thermogenesis and browning of subcutaneous WAT leading to elevated energy expenditure. Moreover, rats experiencing EA showed inhibition of hypothalamic AMPK, a canonical energy sensor modulating energy homeostasis at the central level. Notably, specific genetic activation of AMPK in the ventromedial nucleus of the hypothalamus (a key site modulating energy metabolism) reversed the effect of EA on energy balance, brown fat, and browning, as well as promoting amelioration of synovial inflammation in experimental arthritis. Conclusion: Overall, these data indicate that EA promotes a central catabolic state that can be targeted and reversed by the activation of hypothalamic AMPK. This might provide new therapeutic alternatives to treat rheumatoid arthritis (RA)–associated metabolic comorbidities, improving the overall prognosis in patients with RA
dc.description.sponsorshipThe Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CiMUS) is supported by the Xunta de Galicia (2016-2019, ED431G/05). The Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn) is an initiative of the Instituto de Salud Carlos III. Supported by the Xunta de Galicia (grants 2016-PG057 to Dr. Nogueiras, GPC IN607B2019/10 to Dr. Gualillo, and 2016-PG068 to Dr. López), the Ministerio de Economía y Competitividad (MINECO) co-funded by the FEDER Program of the European Union (grants BFU2017-90578-REDT/Adipoplast to Drs. Fernández-Real and López, RTI2018-099413-B-I00 to Dr. Nogueiras, BFU2017-87721-P to Dr. Diéguez, and RTI2018-101840-B-I00 to Dr. López), the Instituto de Salud Carlos III (grants PI15–01934 and PI18/0102224 to Dr. Fernández-Real and PI17/00409, PI20/00902, RD21/0002/0025, and RD16/0012/0014 to Dr. Gualillo), “la Caixa” Foundation (ID 100010434) (grant LCF/PR/HR19/52160022 to Dr. López), and the European Research Council (synergy grant-2019-WATCH- 810331 to Dr. Nogueiras). Dr. Seoane-Collazo's work was supported by the Xunta de Galicia (fellowship ED481B 2018/050) and the Horizon 2020 Research and Innovation Program of the European Union under the Marie Sklodowska-Curie actions. Drs. Nogueiras and López's work was supported in part by the Atresmedia Corporación. Dr. Nogueiras's work was supported in part by Fundación BBVA and the European Foundation for the Study of Diabetes. Dr. Gualillo's work was supported in part by the Horizon 2020 Research and Innovation Program of the European Union under the Marie Sklodowska-Curie actions (project no. 734899) and by the Xunta de Galicia through a research staff contract (ISCIII/SERGAS)
dc.language.isoeng
dc.publisherWiley
dc.rights© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleActivation of hypothalamic AMP-activated protein kinase ameliorates metabolic complications of experimental arthritis
dc.typejournal article
dc.identifier.doi10.1002/art.41950
dc.relation.publisherversionhttps://doi.org/10.1002/art.41950
dc.type.hasVersionVoR
dc.identifier.essn2326-5205
dc.rights.accessRightsopen access
dc.contributor.affiliationUniversidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas
dc.contributor.affiliationUniversidade de Santiago de Compostela. Departamento de Ciencias Morfolóxicas
dc.contributor.affiliationUniversidade de Santiago de Compostela. Departamento de Fisioloxía
dc.description.peerreviewedSI


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© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made
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 © 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made





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