Irisin Attenuates Muscle Impairment during Bed Rest through Muscle-Adipose Tissue Crosstalk

SIMPLE SUMMARY: Irisin is a known myokine secreted mainly by the muscle that is produced after physical activity. It induces browning in the adipose tissue with a consequent increase in mitochondrial oxidation of lipids and reduction of insulin resistance; thus, it has been hypothesized that irisin was the molecule mediating most of the beneficial effects related to exercise on adipose tissue and consequently on the whole organism. In our study we observed that extreme physical inactivity induces the loss of muscle mass and function, and an increase in the body adipose tissue as expected. However, of note, circulating irisin levels were increased secondary to enhanced irisin synthesis mainly from adipose tissue rather than muscle. In addition, subjects who produced more irisin had reduced muscle impairment. Therefore, our hypothesis is that there is negative feedback within the muscle-adipose tissue crosstalk, specifically not only does the muscle influence the adipose tissue through irisin during exercise, but also the adipose tissue protects the muscle during inactivity. ABSTRACT: The detrimental effect of physical inactivity on muscle characteristics are well known. Irisin, an exercise-induced myokine cleaved from membrane protein fibronectin type III domain-containing protein-5 (FNDC5), mediates at least partially the metabolic benefits of exercise. This study aimed to assess the interplay between prolonged inactivity, circulating irisin, muscle performance, muscle fibers characteristics, as well as the FNDC5 gene expression (FNDC5ge) in muscle and adipose tissue among healthy subjects. Twenty-three healthy volunteers were tested before and after 14 days of Bed Rest, (BR). Post-BR circulating levels of irisin significantly increased, whereas body composition, muscle performance, and muscle fiber characteristics deteriorated. Among the subjects achieving the highest post-BR increase of irisin, the lowest reduction in maximal voluntary contraction and specific force of Fiber Slow/1, the highest increase of FNDC5ge in adipose tissue, and no variation of FNDC5ge in skeletal muscle were recorded. Subjects who had the highest FNDC5ge in adipose tissue but not in muscle tissue showed the highest circulating irisin levels and could better withstand the harmful effect of BR.