Improved skeletal muscle fatigue resistance in experimental autoimmune myositis mice following high-intensity interval training

Background: Muscle weakness and decreased fatigue resistance are key manifestations of idiopathic inflammatory myopathies (IIMs). We here examined whether high-intensity interval training (HIIT) improves fatigue resistance in skeletal muscle of experimental autoimmune myositis (EAM) mice, a widely used animal model for IIM. Methods Female BALB/c mice were randomly assigned to control (CNT) or EAM groups (n = 28 in each group). EAM was induced by immunization with three injections of myosin emulsified in complete Freund’s adjuvant. The plantar flexor (PF) muscles from mice with EAM were exposed to either an acute bout or 4 weeks of HIIT (a total of 14 sessions). Results The fatigue resistance of PF muscles was lower in the EAM than in the CNT group ( P  < 0.05). These changes were associated with decreased activities of citrate synthase and cytochrome c oxidase and increased expression levels of the endoplasmic reticulum stress proteins (glucose-regulated protein 78 and 94, and PKR-like ER kinase) ( P  < 0.05). HIIT restored all these alterations and increased the peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α) and the mitochondrial electron transport chain complexes (I, III, and IV) in muscles from EAM mice ( P  < 0.05). Conclusions HIIT improves fatigue resistance in an IIM mouse model and this can be explained by restoration of mitochondria oxidative capacity via inhibition of the ER stress pathway and PGC-1α-mediated mitochondrial biogenesis.