The "irisin system": From biological roles to pharmacological and nutraceutical perspectives

The scientific interest in irisin, a myokine discovered in 2012, has grown exponentially in recent years. Irisin, which is mainly produced in skeletal muscle, influences the browning process of adipose tissue and lipid and energy metabolism. Recent discoveries highlight that the potential of this hormone may have been underestimated. In the first part of this review, reports on irisin structure and molecules involved in its metabolic pathway are shown. Furthermore, data related to unclear aspects are also reported: distribution, different gene expression of its precursors in different tissues, physiological levels of circulating irisin, and pharmacokinetic and pharmacodynamic profile. The second part of this work focuses on exogenous stimuli and pharmacological agents which regulate the metabolic pathway of irisin and its serum concentration. In addition to physical exercise and exposure to low temperatures, which were early recognized as exogenous stimuli able to promote the production of this myokine, preclinical and clinical evidence demonstrates the ability of natural and synthetic molecules to interfere with this metabolic pathway. Current experimental data on irisin cannot dissolve all doubts related to this interesting molecule, but they certainly underline its potential for therapeutic purposes. Thus, identification of new pharmacological tools able to act on the irisin pathway is a challenging issue for biomedical research.