Skeletal muscle mitochondrial responses to a single bout and six weeks of high load versus high volume resistance training in previously trained men

Mueller, B.; Fox, C. D.; Parry, H. A.; Mesquita, P. H. C.; Vann, C. G.; Ruple, B. A.; Sexton, C. L.; Godwin, J. S.; McIntosh, M. M.; Beck, D. T.; Young, K. C.; Phillips, S. M.; Kavazis, A. N.; Roberts, M. D.

doi:10.1101/2025.07.23.666423

bioRxiv · 10.1101/2025.07.23.666423

Skeletal muscle mitochondrial responses to a single bout and six weeks of high load versus high volume resistance training in previously trained men

Mueller, B.·Fox, C. D.·Parry, H. A.·Mesquita, P. H. C.·Vann, C. G.·Ruple, B. A.·Sexton, C. L.·Godwin, J. S.·McIntosh, M. M.·Beck, D. T.·Young, K. C.·Phillips, S. M.·Kavazis, A. N.·Roberts, M. D.

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Abstract

The effects of higher-load (HL) versus higher-volume (HV) resistance training (RT) on various molecular outcomes are similar. However, mitochondrial responses remain understudied. Therefore, the purpose of this study was to interrogate mitochondrial mRNA and protein responses to acute and chronic HL versus HV RT. Vastus lateralis biopsies from resistance trained males in two prior studies were assessed. In STUDY 1, 11 college-aged men completed an acute bout of either HL or HV RT exercises to failure. Biopsies were collected at PRE, 3 hours post-, and 6 hours post-exercise. In STUDY 2, 15 college-aged men participated in six weeks of supervised unilateral RT where each leg was assigned to either HL or HV RT. Biopsies were collected from both legs prior to and 72 hours following last training bout of the intervention. Biopsies from both studies were used to assess mitochondrial mRNAs, and STUDY 2 biopsies were assayed for mitochondrial proteins and CS activity. Results from both studies revealed several significant main effects of time but no significant interactions. Additionally, CS activity, a surrogate of mitochondrial content, decreased following chronic RT (p=0.016) but no interaction was observed between the HV and HL leg over time (p=0.882). In conclusion, while RT resulted in both acute mitochondrial mRNA as well as chronic CS activity and mitochondrial protein responses, there were no differences in the HL versus HV paradigms on these outcomes.

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Mueller, B., Fox, C. D., Parry, H. A., Mesquita, P. H. C., Vann, C. G., Ruple, B. A., Sexton, C. L., Godwin, J. S., McIntosh, M. M., Beck, D. T., Young, K. C., Phillips, S. M., Kavazis, A. N., Roberts, M. D.. 2025-07-29. Skeletal muscle mitochondrial responses to a single bout and six weeks of high load versus high volume resistance training in previously trained men. https://doi.org/10.1101/2025.07.23.666423

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