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In this study, we compared the effects of repeated IT100 and IT20 on fatigue resistance and mitochondrial adaptations in young male mdx52 mice (4\u2010 to 6\u2010week\u2010old), an animal model for Duchenne muscular dystrophy. Plantar flexor muscles were stimulated in\u00a0vivo using supramaximal electrical stimulation to induce isometric contractions every other day for 4\u2009weeks (a total of 15 sessions). In non\u2010trained muscles of mdx52 mice, decreased fatigue resistance was associated with reduced citrate synthase activity, lower peroxisome proliferator\u2010activated receptor \u03b3 coactivator 1 alpha (PGC\u20101\u03b1) protein expression, and diminished levels of mitochondrial respiratory chain complex II, and an increased percentage of Evans Blue dye\u2010positive areas. IT100, but not IT20, markedly improved fatigue resistance and restored all these alterations in mdx52 mice. Furthermore, an acute session of IT100, but not IT20, led to increased phosphorylation of p38 mitogen\u2010activated protein kinase (MAPK) and elevated mRNA levels of PGC\u20101\u03b1, which were blocked by the p38 MAPK inhibitor SB203580. These findings suggest that contractile load is a key determinant of isometric IT\u2010induced improvements in fatigue resistance, even in dystrophin\u2010deficient muscles, potentially through a p38 MAPK\/PGC\u20101\u03b1\u2010mediated increase in mitochondrial content.<\/jats:p>","DOI":"10.1096\/fj.202500618rr","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T09:39:51Z","timestamp":1747215591000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Fatigue Resistance and Mitochondrial Adaptations to Isometric Interval Training in Dystrophin\u2010Deficient Muscle: Role of Contractile Load"],"prefix":"10.1096","volume":"39","author":[{"given":"Nao","family":"Yamauchi","sequence":"first","affiliation":[{"name":"Graduate School of Health Sciences Sapporo Medical University  Sapporo Japan"},{"name":"The Japan Society for the Promotion of Science (JSPS)  Tokyo 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