dc.creator | Selvais, Camille M. | es |
dc.creator | Davis López de Carrizosa, María América | es |
dc.creator | Nachit, Maxime | es |
dc.creator | Versele, Romain | es |
dc.creator | Dubuisson, Nicolas | es |
dc.creator | Noel, Laurence | es |
dc.creator | Abou-Samra, Michel | es |
dc.date.accessioned | 2023-12-15T10:17:18Z | |
dc.date.available | 2023-12-15T10:17:18Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Selvais, C.M., Davis López de Carrizosa, M.A., Nachit, M., Versele, R., Dubuisson, N., Noel, L. y Abou-Samra, M. (2023). AdipoRon enhances healthspan in middle‐aged obese mice: striking alleviation of myosteatosis and muscle degenerative markers. Journal Of Cachexia, Sarcopenia and Muscle, 14 (1), 464-478. https://doi.org/10.1002/jcsm.13148. | |
dc.identifier.issn | 2190-5991 | es |
dc.identifier.issn | 2190-6009 | es |
dc.identifier.uri | https://hdl.handle.net/11441/152541 | |
dc.description.abstract | BackgroundObesity among older adults has increased tremendously. Obesity accelerates ageing and predisposes toage-related conditions and diseases, such as loss of endurance capacity, insulin resistance and features of the metabolicsyndrome. Namely, ectopic lipids play a key role in the development of nonalcoholic fatty liver disease (NAFLD) andmyosteatosis, two severe burdens of ageing and metabolic diseases. Adiponectin (ApN) is a hormone, mainly secretedby adipocytes, which exerts insulin-sensitizing and fat-burning properties in several tissues including the liver and themuscle. Its overexpression also increases lifespan in mice. In this study, we investigated whether an ApN receptor ag-onist, AdipoRon (AR), could slow muscle dysfunction, myosteatosis and degenerative muscle markers in middle-agedobese mice. The effects on myosteatosis were compared with those on NAFLD.MethodsThree groups of mice were studied up to 62 weeks of age: One group received normal diet (ND), another,high-fat diet (HFD); and the last, HFD combined with AR given orally for almost 1 year. An additional group of youngmice under an ND was used. Treadmill tests and micro-computed tomography (CT) were carried out in vivo. Histolog-ical, biochemical and molecular analyses were performed on tissues ex vivo. Bodipy staining was used to assessintramyocellular lipid (IMCL) and lipid droplet morphology.ResultsAR did not markedly alter diet-induced obesity. Yet, this treatment rescued exercise endurance in obese mice(up to 2.4-fold,P<0.05), an event that preceded the improvement of insulin sensitivity. Dorsal muscles and liver den-sities, measured by CT, were reduced in obese mice ( 42% and 109%, respectively,P<0.0001), suggesting fatty in-filtration. This reduction tended to be attenuated by AR. Accordingly, AR significantly mitigated steatosis and cellularballooning at liver histology, thereby decreasing the NALFD activity score ( 30%,P<0.05). AR also strikingly reversedIMCL accumulation either due to ageing in oxidativefibres (types 1/2a, soleus) or to HFD in glycolytic ones (types2x/2b, extensor digitorum longus) ( 50% to 85%,P<0.05 or less). Size of subsarcolemmal lipid droplets, knownto be associated with adverse metabolic outcomes, was reduced as well. Alleviation of myosteatosis resulted from im-proved mitochondrial function and lipid oxidation. Meanwhile, AR halved aged-related accumulation of dysfunctionalproteins identified as tubular aggregates and cylindrical spirals by electron microscopy (P<0.05).ConclusionsLong-term AdipoRon treatment promotes‘healthy ageing’in obese middle-aged mice by enhancing en-durance and protecting skeletal muscle and liver against the adverse metabolic and degenerative effects of ageingand caloric excess. | es |
dc.description.sponsorship | University College de Londres (UCL) de Reino Unido - FSR 2017 | es |
dc.description.sponsorship | Société Francophone du Diabète de Francia/Roche Diabetes Care de España 2020 | es |
dc.description.sponsorship | National Fund for Scientific Research de Bélgica - FNRS 35275437, 2019 | es |
dc.format | application/pdf | es |
dc.format.extent | 15 p. | es |
dc.language.iso | eng | es |
dc.publisher | Wiley Open Access | es |
dc.relation.ispartof | Journal Of Cachexia, Sarcopenia and Muscle, 14 (1), 464-478. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | adiponectin | es |
dc.subject | myosteatosis | es |
dc.subject | intramyocellular lipids | es |
dc.subject | ageing | es |
dc.subject | nonalcoholic fatty liver disease | es |
dc.subject | endurance | es |
dc.title | AdipoRon enhances healthspan in middle‐aged obese mice: striking alleviation of myosteatosis and muscle degenerative markers | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Fisiología | es |
dc.relation.projectID | FSR 2017 | es |
dc.relation.projectID | FNRS 35275437, 2019 | es |
dc.relation.publisherversion | https://doi.org/10.1002/jcsm.13148 | es |
dc.identifier.doi | 10.1002/jcsm.13148 | es |
dc.journaltitle | Journal Of Cachexia, Sarcopenia and Muscle | es |
dc.publication.volumen | 14 | es |
dc.publication.issue | 1 | es |
dc.publication.initialPage | 464 | es |
dc.publication.endPage | 478 | es |
dc.contributor.funder | University College de Londres (UCL). UK | es |
dc.contributor.funder | Société Francophone du Diabète (SFD). Francia | es |
dc.contributor.funder | National Fund for Scientific Research (FNRS). Bélgica | es |