{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:08:00Z","timestamp":1790842080755,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T00:00:00Z","timestamp":1579564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006282","name":"Koning Boudewijnstichting","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006282","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":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Adiponectin (ApN) is a hormone known to exhibit insulin\u2010sensitizing, fat\u2010burning, and anti\u2010inflammatory properties in several tissues, including the skeletal muscle. Duchenne muscular dystrophy (DMD) is a devastating disease characterized by dystrophin deficiency with subsequent chronic inflammation, myofiber necrosis, and impaired regeneration. Previously, we showed that transgenic up\u2010regulation of ApN could significantly attenuate the dystrophic phenotype in mdx mice (model of DMD). Recently, an orally active ApN receptor agonist, AdipoRon, has been identified. This synthetic small molecule has the advantage of being more easily produced and administrable than ApN. The aim of this study was to investigate the potential effects of AdipoRon on the dystrophic muscle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four\u2010week\u2010old mdx mice (<jats:italic>n<\/jats:italic> = 6\u20139 per group) were orally treated with AdipoRon (mdx\u2010AR) for 8 weeks and compared with untreated (mdx) mice and to control (wild\u2010type) mice. <jats:italic>In vivo<\/jats:italic> functional tests were carried out to measure the global force and endurance of mice. <jats:italic>Ex vivo<\/jats:italic> biochemical and molecular analyses were performed to evaluate the pathophysiology of the skeletal muscle. Finally, <jats:italic>in vitro<\/jats:italic> tests were conducted on primary cultures of healthy and DMD human myotubes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AdipoRon treatment mitigated oxidative stress (\u221230% to 45% for 4\u2010hydroxy\u20102\u2010nonenal and peroxiredoxin 3, <jats:italic>P<\/jats:italic> &lt; 0.0001) as well as inflammation in muscles of mdx mice (\u221235% to 65% for interleukin 1 beta, tumour necrosis factor alpha, and cluster of differentiation 68, a macrophage maker, <jats:italic>P<\/jats:italic> &lt; 0.0001) while increasing the anti\u2010inflammatory cytokine, interleukin 10 (~5\u2010fold, <jats:italic>P<\/jats:italic> &lt; 0.0001). AdipoRon also improved the myogenic programme as assessed by a ~2\u2010fold rise in markers of muscle proliferation and differentiation (<jats:italic>P<\/jats:italic> &lt; 0.01 or less vs. untreated mdx). Plasma lactate dehydrogenase and creatine kinase were reduced by 30\u201340% in mdx\u2010AR mice, reflecting less sarcolemmal damage (<jats:italic>P<\/jats:italic> &lt; 0.0001). When compared with untreated mdx mice, mdx\u2010AR mice exhibited enhanced physical performance with an increase in both muscle force and endurance and a striking restoration of the running capacity during eccentric exercise. AdipoRon mainly acted through ApN receptor 1 by increasing AMP\u2010activated protein kinase signalling, which led to repression of nuclear factor\u2010kappa B, up\u2010regulation of utrophin (a dystrophin analogue), and a switch towards an oxidative and more resistant fibre phenotype. The effects of AdipoRon were then recapitulated in human DMD myotubes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results demonstrate that AdipoRon exerts several beneficial effects on the dystrophic muscle. This molecule could offer promising therapeutic prospect for managing DMD or other muscle and inflammatory disorders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12531","type":"journal-article","created":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T05:16:14Z","timestamp":1579670174000},"page":"518-533","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["<scp>AdipoRon<\/scp>, a new therapeutic prospect for Duchenne muscular dystrophy"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2312-7998","authenticated-orcid":false,"given":"Michel","family":"Abou\u2010Samra","sequence":"first","affiliation":[{"name":"Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Medical Sector Universit\u00e9 Catholique de Louvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille M.","family":"Selvais","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Medical Sector Universit\u00e9 Catholique de Louvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Boursereau","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Medical Sector Universit\u00e9 Catholique de Louvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Lecompte","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Medical Sector Universit\u00e9 Catholique de Louvain  Brussels 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