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

Abstract 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.