Comparative proteome analyses highlight several exercise‐like responses of mouse sciatic nerve after IP injection of irisin

Many beneficial effects of exercise on the nervous system are mediated by hormone (growth factor)/receptor signaling. Considering the accumulating evidence on the similarity of some beneficial effects, irisin can be a proposed effector of exercise; however, the mechanism underlying these effects remains largely unknown. More evidence on the mechanism of action might reveal its potential as a treatment strategy to substitute exercise recovery protocols for nerve injuries in physically disabled patients. To evaluate the underlying mechanism of irisin involvement in nerve adaptation and exerting beneficial effects, we studied the proteome profile alteration of mouse sciatic nerve after irisin administration. We also compared it with two 8‐week protocols of resistance exercise and endurance exercise. The results indicate that irisin contributes to the regulation of nerve metabolism via overexpression of Ckm and ATP5j2 proteins. Irisin administration may improve sciatic nerve function by maintaining the architecture, enhancing axonal transport, and promoting synapse plasticity through increased structural and regulatory proteins and NO production. We also showed that irisin has the potential to induce neurotrophic support on the sciatic nerve by maintaining cell redox homeostasis, and responses to oxidative stress via the upregulation of disulfide‐isomerase and superoxide dismutase enzymes. Comparing with exercise groups, these effects are somewhat exercise‐like responses. These data suggest that irisin can be a promising therapeutic candidate for specific targeting of defects in peripheral neuropathies and nerve injuries as an alternative for physical therapy. Irisin is recently suggested as an exercise mediator, and this study highlights several molecular effects of irisin injection on mouse sciatic nerve. Irisin seems to regulate nerve energy and metabolism. It increases the structural and regulatory proteins and enzymes that are involved in the architecture and integrity of the nerve, axonal transport, and neurotransmitter production. It is proposed to have neurotrophic effects due to inducing the upregulation of P4hb and Sod1 proteins. Compared with exercise groups, these effects are somewhat exercise‐like responses.