Irisin and musculoskeletal health

Abstract Irisin is a hormone‐like myokine produced in abundance by skeletal muscle in response to exercise, both in mice and humans. Once released into the circulation, irisin acts on white adipocytes to induce the browning response and subsequently activates nonshivering thermogenesis. We have examined the premise that irisin produced during exercise may subserve further functions in the musculoskeletal system. We review evidence for its possible skeletal effects, including the central role that irisin plays in the control of bone mass, with positive effects on cortical mineral density and geometry in mice. We also review the autocrine effects of irisin in skeletal muscle, in which it upregulates the expression of its precursor (FNDC5). Since loss of bone and muscle mass occurs with aging, immobility, and several metabolic diseases, future studies exploring the efficacy of irisin in restoring bone and reversing muscle wasting could be important to establishing irisin as a molecule that combines beneficial effects for treating osteoporosis and muscular atrophy. If the results from mice were confirmed in human studies, an irisin‐based therapy could be developed for physically disabled or bedridden patients.