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

Abstract

Background Muscle weakness and decreased fatigue resistance are key manifestations of systemic autoimmune myopathies (SAMs). We here examined whether high-intensity interval training (HIIT) improves fatigue resistance in the skeletal muscle of experimental autoimmune myositis (EAM) mice, a widely used animal model for SAM. 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 of 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 the muscles of EAM mice (P < 0.05). Conclusions HIIT improves fatigue resistance in a SAM mouse model, and this can be explained by the restoration of mitochondria oxidative capacity via inhibition of the ER stress pathway and PGC-1α-mediated mitochondrial biogenesis.

High‐intensity interval training in the form of isometric contraction improves fatigue resistance in dystrophin‐deficient muscle

“…Importantly, a single bout of HIIT induced the phosphorylation of AMPK and its downstream target ACC, which was associated with restoration of PGC-1α content after 4 weeks of isometric HIIT in muscle from mdx52 mice. These results fit with our previous studies where the same isometric HIIT protocol activates the AMPK/PGC-1α pathway and improves fatigue resistance in normal (Yamada et al, 2021) and experimental autoimmune myositis (Yamada et al, 2022) mice. More surprisingly, the magnitude of increase in PGC-1α content, CS activity and fatigue resistance was almost similar with WT and mdx52 mice, indicating that AMPK-dependent improvement of mitochondrial oxidative capacity can be caused by HIIT even in dystrophic conditions.…”

“…The stimulation scheme was designed to mimic the activation pattern during an all-out cycling bouts, i.e. 0.25 s tetanic contractions at a stimulation frequency of 100 Hz produced every 0.5 s (Place et al, 2015;Yamada et al, 2021Yamada et al, , 2022. Each session consisted of six sets of 60 contractions at 4-min intervals.…”

“…Emerging evidence shows that high‐intensity interval training (HIIT) is an effective way to improve fatigue resistance in healthy individuals and diseased populations (Gibala et al., 2012). We have recently demonstrated that HIIT‐mimicking neuromuscular electrical stimulation in the form of isometric contraction improves resistance to fatigue accompanied by AMPK‐dependent increase in mitochondrial capacity in normal (Yamada et al., 2021) and experimental autoimmune myositis mice (Yamada et al., 2022). Therefore, the objective of the current study was to test the hypothesis that HIIT with isometric contractions improves fatigue resistance in dystrophic muscle via AMPK‐dependent de novo mitochondrial biogenesis and induction of mitophagy.…”

Platelet‐rich plasma does not accelerate the healing of damaged muscle following muscle strain

“…All statistics were performed on Graphpad prism 8 and differences were considered statistically significant at p < 0.05 (*). A power analysis was performed on data from our previously published work 9 using SigmaPlot (version 13, Systat Software, Inc.), assuming changes in physiological measurements for PRP groups being 30 ± 20% of the value for the PBS group. With a power of 0.80 and an ⍺ of 0.05, this gives a sample size of five.…”

The Emerging Role of Mitochondrial Dysfunction in the Pathogenesis of Idiopathic Inflammatory Myopathies

“… 110 Animal models have revealed that exercise is able to lessen the release of cytochrome c from mitochondria to the myocyte’s cytoplasm, reduce the amyloid-β accumulation that is believed to be responsible for mitochondrial biogenesis disruption, and enhance mitochondrial respiratory capacity by increasing the expression of respiratory complexes I, III, and IV. 145 – 147 …”