{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:45:15Z","timestamp":1788777915994,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T00:00:00Z","timestamp":1671753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K15069"],"award-info":[{"award-number":["18K15069"]}],"id":[{"id":"10.13039\/501100001691","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":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Targeting of the apelin\u2013apelin receptor (Apj) system may serve as a useful therapeutic intervention for the management of chronic kidney disease (CKD)\u2010induced skeletal muscle atrophy. We investigated the roles and efficacy of the apelin\u2013Apj system in CKD\u2010induced skeletal muscle atrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The 5\/6\u2010nephrectomized mice were used as CKD models. AST\u2010120, a charcoal adsorbent of uraemic toxins (8 w\/w% in diet), or apelin (1\u00a0\u03bcmol\/kg) was administered to CKD mice to investigate the mechanism and therapeutic potential of apelin on CKD\u2010induced skeletal muscle atrophy. The effect of indoxyl sulfate, a uraemic toxin, or apelin on skeletal muscle atrophy was evaluated using mouse myoblast cells (C2C12 cells) in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Skeletal muscle atrophy developed over time following nephrectomy at 12\u00a0weeks, as confirmed by a significant increase of atrogin\u20101 and myostatin mRNA expression in the gastrocnemius (GA) muscle and a decrease of lower limb skeletal muscle weight (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05, 0.01 and 0.05, respectively). Apelin expression in GA muscle was significantly decreased (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and elabela, another Apj endogenous ligand, tended to show a non\u2010significant decrease at 12\u00a0weeks after nephrectomy. Administration of AST\u2010120 inhibited the decline of muscle weight and increase of atrogin\u20101 and myostatin expression. Apelin and elabela expression was slightly improved by AST\u2010120 administration but Apj expression was not, suggesting the involvement of uraemic toxins in endogenous Apj ligand expression. The administration of apelin at 1.0\u00a0\u03bcmol\/kg for 4\u00a0weeks to CKD mice suppressed the increase of atrogin\u20101 and myostatin, increased apelin and Apj mRNA expression at 30\u00a0min after apelin administration and significantly ameliorated weight loss and a decrease of the cross\u2010sectional area of hindlimb skeletal muscle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrated for the first time the association of the Apj endogenous ligand\u2013uraemic toxin axis with skeletal muscle atrophy in CKD and the utility of therapeutic targeting of the apelin\u2013Apj system.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13159","type":"journal-article","created":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T09:44:35Z","timestamp":1671788675000},"page":"553-564","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The G protein\u2010coupled receptor ligand apelin\u201013 ameliorates skeletal muscle atrophy induced by chronic kidney disease"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5934-0670","authenticated-orcid":false,"given":"Yuki","family":"Enoki","sequence":"first","affiliation":[{"name":"Division of Pharmacodynamics Keio University Faculty of Pharmacy  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoya","family":"Nagai","sequence":"additional","affiliation":[{"name":"Division of Pharmacodynamics Keio University Faculty of Pharmacy  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuna","family":"Hamamura","sequence":"additional","affiliation":[{"name":"Division of Pharmacodynamics Keio University Faculty of Pharmacy  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumika","family":"Osa","sequence":"additional","affiliation":[{"name":"Division of Pharmacodynamics Keio University Faculty of Pharmacy  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