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Research Square
Yamada, T;Ashida, Y;Tamai, K;Kimura, I;Yamauchi, N;Naito, A;Tokuda, N;Westerblad, H;Andersson, D;Himori, K;
Abstract
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.