Resistance exercise-induced circulating factors influence the damaged skeletal muscle proteome in a sex-dependent manner.

Muscle recovery after damage is mediated by circulating factors and intracellular signaling pathways. Our previous studies have demonstrated that resistance exercise (RE)-induced circulating factors elicited sex-differential responses in damaged muscle. However, the global effects of these circulating factors on damaged muscle are largely understudied. We examined the differential effects of RE-induced circulating factors and sex on the damaged muscle proteome. Damaged vastus lateralis muscle from 3 men and 3 women from a parent study were analyzed. Participants completed 2 identical bouts of unilateral eccentric knee extensions immediately followed by either upper body RE to induce circulating factors (EXE) or 20-min seated rest (CON). Muscle biopsies collected from the damaged leg at 24 h were used. 900 proteins were identified by LC-MS/MS analysis. Ingenuity Pathway Analysis was used to detect activation prediction using z-scores for functional and pathway analyses. In men, 79 proteins were downregulated and 15 were upregulated in EXE versus CON. These differentially expressed proteins were associated with immunological and inflammatory signaling pathways. Biological functions of the differentially expressed proteins in EXE vs. CON in men include inactivating acute inflammatory signaling, neutrophil extracellular trap signaling, ROS production, and activating IL-12 signaling. These results underline that RE-induced circulating factors have a sex-specific effect on the damaged muscle proteome, where immune signaling is altered in men but not women. Given that the immune response is critical for recovery from muscle damage, these results highlight the potential role of RE-induced circulating factors that could be essential in mediating muscle recovery.