{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T19:22:47Z","timestamp":1780600967511,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:00:00Z","timestamp":1712188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","award":["7450318"],"award-info":[{"award-number":["7450318"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","award":["7652020"],"award-info":[{"award-number":["7652020"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cancer cachexia is a life\u2010threatening, inflammation\u2010driven wasting syndrome that remains untreatable. Adiponectin, the most abundant adipokine, plays an important role in several metabolic processes as well as in inflammation modulation. Our aim was to test whether administration of AdipoRon (AR), a synthetic agonist of the adiponectin receptors, prevents the development of cancer cachexia and its related muscle atrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The effect of AR on cancer cachexia was investigated in two distinct murine models of colorectal cancer. First, 7\u2010week\u2010old CD2F1 male mice were subcutaneously injected with colon\u201026 carcinoma cells (C26) or vehicle (CT). Six days after injection, mice were treated for 5\u00a0days with AdipoRon (50\u00a0mg\/kg\/day; C26\u00a0+\u00a0AR) or the corresponding vehicle (CT and C26). Additionally, a genetic model, the Apc<jats:sup><jats:italic>Min<\/jats:italic>\/+<\/jats:sup> mouse, that develops spontaneously numerous intestinal polyps, was used. Eight\u2010week\u2010old male Apc<jats:sup><jats:italic>Min\/+<\/jats:italic><\/jats:sup> mice were treated with AdipoRon (50\u00a0mg\/kg\/day; Apc\u00a0+\u00a0AR) or the corresponding vehicle (Apc) over a period of 12\u00a0weeks, with C57BL\/6J wild\u2010type mice used as controls. In both models, several parameters were assessed in vivo: body weight, grip strength and serum parameters, as well as ex vivo: molecular changes in muscle, fat and liver.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The protective effect of AR on cachexia development was observed in both cachectic C26 and Apc<jats:sup><jats:italic>Min<\/jats:italic>\/+<\/jats:sup> mice. In these mice, AR administration led to a significant alleviation of body weight loss and muscle wasting, together with rescued muscle strength (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 for all). In both models, AR had a strong anti\u2010inflammatory effect, reflected by lower systemic interleukin\u20106 levels (\u221255% vs. C26, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001 and \u221280% vs. Apc mice, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), reduced muscular inflammation as indicated by lower levels of <jats:italic>Socs3<\/jats:italic>, phospho\u2010STAT3 and <jats:italic>Serpina3n<\/jats:italic>, an acute phase reactant (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 for all). In addition, AR blunted circulating levels of corticosterone (\u221246% vs. C26 mice, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001 and \u221260% vs. Apc mice, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), the predominant murine glucocorticoid known to induce muscle atrophy. Accordingly, key glucocorticoid\u2010responsive factors implicated in atrophy programmes were\u2014or tended to be\u2014significantly blunted in skeletal muscle by AR. Finally, AR protected against lipid metabolism alterations observed in Apc<jats:sup><jats:italic>Min<\/jats:italic>\/+<\/jats:sup> mice, as it mitigated the increase in circulating triglyceride levels (\u221238%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) by attenuating hepatic triglyceride synthesis and fatty acid uptake by the liver.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Altogether, these results show that AdipoRon rescued the cachectic phenotype by alleviating body weight loss and muscle atrophy, along with restraining inflammation and hypercorticism in preclinical murine models. Therefore, AdipoRon could represent an innovative therapeutic strategy to counteract cancer cachexia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13454","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T07:46:33Z","timestamp":1712216793000},"page":"919-933","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Administration of adiponectin receptor agonist AdipoRon relieves cancer cachexia by mitigating inflammation in tumour\u2010bearing mice"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5620-9557","authenticated-orcid":false,"given":"Isabelle S.","family":"Massart","sequence":"first","affiliation":[{"name":"Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research Universit\u00e9 catholique de Louvain  Brussels 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