{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T13:13:16Z","timestamp":1793797996687,"version":"4.6.1"},"reference-count":54,"publisher":"Canadian Science Publishing","issue":"9","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/deed.en_GB"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Appl. Physiol. Nutr. Metab."],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:p> Cancer cachexia (CC) accounts for 20%\u201340% of cancer-related deaths. Mitochondrial aberrations have been shown to precede muscle atrophy in different atrophy models, including cancer. Therefore, this study investigated potential protection from the cachectic phenotype through overexpression of peroxisome proliferator-activated receptor \u03b3 coactivator-1 \u03b1 (PGC-1\u03b1). First, to establish potential of mitochondria-based approaches we showed that the mitochondrial antioxidant MitoTEMPO (MitoT) attenuates myotube atrophy induced by Lewis lung carcinoma (LLC) cell conditioned media. Next, cachexia was induced in muscle-specific PGC-1\u03b1 overexpressing (MCK-PCG1\u03b1) or wildtype (WT) littermate mice by LLC implantation. MCK-PCG1\u03b1 did not protect LLC-induced muscle mass loss. In plantaris, Atrogin mRNA content was 6.2-fold and \u223c11-fold greater in WT-LLC vs WT-phosphate-buffered saline (PBS) for males and females, respectively ( p\u00a0&lt;\u00a00.05). MitoTimer red:green ratio for male PGC was \u223c65% higher than WT groups ( p\u00a0&lt;\u00a00.05), with \u223c3-fold more red puncta in LLC than PBS ( p\u00a0&lt;\u00a00.05). Red:green ratio was \u223c56% lower in females WT-LLC vs PGC-LLC ( p\u00a0&lt;\u00a00.05). In females, no change in red puncta was noted across conditions. Lc3 mRNA content was \u223c73% and 2-fold higher in male and female LLC mice, respectively, vs PBS ( p\u00a0&lt;\u00a00.05). While MitoT could mitigate cancer-induced atrophy in vitro, PGC-1\u03b1 overexpression was insufficient to protect muscle mass and mitochondrial health in vivo despite mitigation of cachexia-associated signaling pathways. <\/jats:p>","DOI":"10.1139\/apnm-2022-0086","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T21:38:57Z","timestamp":1655242737000},"page":"933-948","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["PGC-1\u03b1 overexpression is not sufficient to mitigate cancer cachexia in either male or female mice"],"prefix":"10.1139","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5019-2125","authenticated-orcid":false,"given":"Francielly","family":"Morena da Silva","sequence":"first","affiliation":[{"name":"Cachexia Research Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation, University of 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