{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:41:08Z","timestamp":1790440868521,"version":"4.1.0"},"reference-count":86,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,11,11]],"date-time":"2017-11-11T00:00:00Z","timestamp":1510358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cancer cachexia is characterized by muscle depletion and exercise intolerance caused by an imbalance between protein synthesis and degradation and by impaired myogenesis. Myofibre metabolic efficiency is crucial so as to assure optimal muscle function. Some drugs are able to reprogram cell metabolism and, in some cases, to enhance metabolic efficiency. Based on these premises, we chose to investigate the ability of the metabolic modulator trimetazidine (TMZ) to counteract skeletal muscle dysfunctions and wasting occurring in cancer cachexia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>For this purpose, we used mice bearing the C26 colon carcinoma as a model of cancer cachexia. Mice received 5\u00a0mg\/kg TMZ (i.p.) once a day for 12 consecutive days. A forelimb grip strength test was performed and <jats:italic>tibialis anterior<\/jats:italic>, and <jats:italic>gastrocnemius<\/jats:italic> muscles were excised for analysis. <jats:italic>Ex vivo<\/jats:italic> measurement of skeletal muscle contractile properties was also performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our data showed that TMZ induces some effects typically achieved through exercise, among which is grip strength increase, an enhanced fast\u2010to slow myofibre phenotype shift, reduced glycaemia, PGC1\u03b1 up\u2010regulation, oxidative metabolism, and mitochondrial biogenesis. TMZ also partially restores the myofibre cross\u2010sectional area in C26\u2010bearing mice, while modulation of autophagy and apoptosis were excluded as mediators of TMZ effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In conclusion, our data show that TMZ acts like an \u2018exercise mimetic\u2019 and is able to enhance some mechanisms of adaptation to stress in cancer cachexia. This makes the modulation of the metabolism, and in particular TMZ, a suitable candidate for a therapeutic rehabilitative protocol design, particularly considering that TMZ has already been approved for clinical use.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12226","type":"journal-article","created":{"date-parts":[[2017,11,11]],"date-time":"2017-11-11T13:16:42Z","timestamp":1510406202000},"page":"954-973","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["The mitochondrial metabolic reprogramming agent trimetazidine as an \u2018exercise mimetic\u2019 in cachectic C26\u2010bearing mice"],"prefix":"10.1002","volume":"8","author":[{"given":"Francesca","family":"Molinari","sequence":"first","affiliation":[{"name":"Laboratory of Pathophysiology of Cachexia and Metabolism of Skeletal Muscle IRCCS San Raffaele Pisana  Via di Val Cannuta 00166 Rome 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