Journal Article

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

Anglin, Derick A., Michel, J. Max, Graham, Zachary A., Bamman, Marcas M., Broderick, Timothy J., Tiede, Dakota R., Plotkin, Daniel L., Roberts, Michael D., Mattingly, Madison L., Bittencourt, Diego, Vann, Christopher G.

2026

Overview

The purpose of this exploratory investigation was to determine if acute post‐exercise skeletal muscle myosin heavy chain fragmentation (MyHCfrag) 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 MyHCfrag post‐exercise was also analysed via bulk RNA‐sequencing. MyHCfrag 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 MyHCfrag. Given these null findings, we explored six participants who experienced the most post‐exercise MyHCfrag versus six who experienced the least MyHCfrag 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‐MyHCfrag participants were related to inflammation. High MyHCfrag 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 MyHCfrag 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. What is the central question of this study? Is myosin heavy chain fragmentation (MyHCfrag) following resistance exercise in humans associated with a physiological signature in skeletal muscle? What is the main finding and its importance? Higher post‐exercise MyHCfrag is associated with a gene signature indicative of inflammation and remodelling. Future research is needed to determine if these acute outcomes translate to meaningful adaptive responses with chronic training.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: Adult / Biopsy / Exercise - physiology / Extracellular matrix / Female / fragmentation / Gene expression / Humans / Inflammation / Inflammation - metabolism / Male / Mechanistic Target of Rapamycin Complex 1 - metabolism / Muscle, Skeletal - metabolism / Musculoskeletal system / Myosin / myosin heavy chain / Myosin Heavy Chains - metabolism / Proteolysis / Proteolytic enzymes / Rapamycin / resistance training / Resistance Training - methods / Signal transduction / Skeletal muscle / TOR protein / Up-regulation / Young Adult