{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:31:27Z","timestamp":1791772287790,"version":"4.3.4"},"reference-count":81,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,10,12]],"date-time":"2019-10-12T00:00:00Z","timestamp":1570838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["11423"],"award-info":[{"award-number":["11423"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["2014-1164"],"award-info":[{"award-number":["2014-1164"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Physical activity improves the prognosis of cancer patients, partly by contrasting the associated muscle wasting (cachexia), through still unknown mechanisms. We asked whether aerobic exercise causes secretion by skeletal muscles of proteins (myokines) that may contrast cachexia. Media conditioned by peroxisome proliferator-activated receptor \u03b3 coactivator 1\u03b1 (PGC1\u03b1)-expressing myotubes, reproducing some metabolic adaptations of aerobic exercise, as increased mitochondrial biogenesis and oxidative phosphorylation, restrained constitutively active Forkhead box-containing subfamily O3 (caFoxO3)-induced proteolysis. Microarray analysis identified amphiregulin (AREG), natriuretic peptide precursor B (NppB), musclin and fibroblast growth factor 18 (FGF18) as myokines highly induced by PGC1\u03b1. Notably, only musclin tended to be low in muscle of mice with a rare human renal carcinoma; it was reduced in plasma and in muscles of C26-bearing mice and in atrophying myotubes, where PGC1\u03b1 expression is impaired. Therefore, we electroporated the Tibialis Anterior (TA) of C26-bearing mice with musclin or (its receptor) natriuretic peptide receptor 3 (Npr3)-encoding plasmids and found a preserved fiber area, as a result of restrained proteolysis. Musclin knockout (KO) mice lose more muscle tissue during growth of two distinct cachexia-causing tumors. Running protected C26-bearing mice from cachexia, not changing tumor growth, and rescued the C26-induced downregulation of musclin in muscles and plasma. Musclin expression did not change in overloaded plantaris of mice, recapitulating partially muscle adaptations to anaerobic exercise. Musclin might, therefore, be beneficial to cancer patients who cannot exercise and are at risk of cachexia and may help to explain how aerobic exercise alleviates cancer-induced muscle wasting.<\/jats:p>","DOI":"10.3390\/cancers11101541","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T03:54:13Z","timestamp":1571025253000},"page":"1541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Musclin, A Myokine Induced by Aerobic Exercise, Retards Muscle Atrophy During Cancer Cachexia in Mice"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1502-9108","authenticated-orcid":false,"given":"Andrea D.","family":"Re Cecconi","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Mario Negri Institute for Pharmacological Research IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Forti","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Mario Negri Institute for Pharmacological Research IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6177-4796","authenticated-orcid":false,"given":"Michela","family":"Chiappa","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Mario Negri Institute for Pharmacological Research IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA"},{"name":"Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA"},{"name":"Department of Medicine, Medical Center, Department of Veterans Affairs, Iowa City, IA 52246, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonid V.","family":"Zingman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA"},{"name":"Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA"},{"name":"Department of Medicine, Medical Center, Department of Veterans Affairs, Iowa City, IA 52246, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Cervo","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Mario Negri Institute for Pharmacological Research IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3631-6544","authenticated-orcid":false,"given":"Luca","family":"Beltrame","sequence":"additional","affiliation":[{"name":"Department of Oncology, Mario Negri Institute for Pharmacological Research IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Marchini","sequence":"additional","affiliation":[{"name":"Department of Oncology, Mario Negri Institute for Pharmacological Research IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1613-9352","authenticated-orcid":false,"given":"Rosanna","family":"Piccirillo","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Mario Negri Institute for Pharmacological Research IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/jso.2930130205","article-title":"An Investigation of the Cause of Death from Cancer","volume":"13","author":"Houten","year":"1980","journal-title":"J. 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