Skeletal muscle myosin heavy chain fragmentation following exercise may be linked to post‐exercise inflammation and remodelling

The purpose of this exploratory investigation was to determine if acute post-exercise skeletal muscle myosin heavy chain fragmentation (MyHC_frag) coincides with alterations in molecular chaperones and proteolytic enzymes, select markers of mammalian target of rapamycin complex 1 (mTORC1) signalling, and/or specific gene expression signatures. Untrained males (n = 10, 23 ± 2 years) and females (n = 10, 23 ± 3 years) completed a bout of combined endurance and resistance exercise. Vastus lateralis muscle biopsies were taken before, 3 h and 24 h post-exercise. Tissue was fractioned into myofibrillar (MF) and sarcoplasmic protein (SF) fractions for protein analysis. Differential RNA expression (DE) from those who experienced high and low MyHC_frag post-exercise was also analysed via bulk RNA-sequencing. MyHC_frag increased 24 h post-exercise, albeit only four of 20 chaperone and proteolytic markers were concomitantly altered and none significantly correlated with 24 h post-exercise MyHC_frag. Given these null findings, we explored six participants who experienced the most post-exercise MyHC_frag versus six who experienced the least MyHC_frag with the intent of examining if post-exercise gene signatures or signalling differed. Although mTORC1 signalling markers were similar, 799 DE transcripts were identified 24 h post-exercise. Pathway analysis on DE differences indicated that nine of the top 10 pathways enriched in high-MyHC_frag participants were related to inflammation. High MyHC_frag participants also presented an upregulation in extracellular matrix remodelling genes at the 24 h post-exercise time point. Though we lack immunohistochemical data, these findings suggest that post-exercise MyHC_frag is associated with an upregulation in an inflammatory and remodelling signature, and longer-term studies are needed to determine if these acute outcomes align with unique adaptive responses.