Regulation of Small RNAs by Exercise and Their Role in Insulin Sensitivity

Vann, C. G.; Bareja, A.; Hubal, M. J.; Naz, S. I.; Ma, S.; Orenduff, M. C.; Ross, L. M.; Bennett, W. C.; Huffman, K. M.; Aliferis, C. F.; Kraus, W.; Kraus, V. B.

doi:10.64898/2026.05.12.724616

bioRxiv · 10.64898/2026.05.12.724616

Regulation of Small RNAs by Exercise and Their Role in Insulin Sensitivity

Vann, C. G.·Bareja, A.·Hubal, M. J.·Naz, S. I.·Ma, S.·Orenduff, M. C.·Ross, L. M.·Bennett, W. C.·Huffman, K. M.·Aliferis, C. F.·Kraus, W.·Kraus, V. B.

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Abstract

We investigated effects of three aerobic exercise interventions, varying in amount and intensity with durations of 8-9-months on small RNA (smRNA) expression and regulatory pathways in skeletal muscle and plasma from 120 participants. Using untargeted smRNA sequencing focused on miRNAs and piRNAs, adjusting for demographics and bodyweight, we identified 124 muscle smRNAs altered by exercise amount and 15 by intensity, and 47 plasma smRNAs altered by intensity and one by amount. These smRNAs were enriched in metabolic, transcriptional, translational, and cell cycle pathways. Exercise-induced changes in several smRNAs-six from muscle and five from plasma-and exercise-induced reduction in body weight, aligned with improvement in insulin sensitivity (p<0.05). These findings demonstrate tissue-specific regulation of smRNAs by exercise and identify potential candidates for exercise mimetics to modulate muscle insulin sensitivity.

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Vann, C. G., Bareja, A., Hubal, M. J., Naz, S. I., Ma, S., Orenduff, M. C., Ross, L. M., Bennett, W. C., Huffman, K. M., Aliferis, C. F., Kraus, W., Kraus, V. B.. 2026-05-17. Regulation of Small RNAs by Exercise and Their Role in Insulin Sensitivity. https://doi.org/10.64898/2026.05.12.724616

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