Irisin in metabolic diseases

Stergios A. Polyzos, Athanasios D. Anastasilakis, Zoe A. Efstathiadou, Polyzois Makras, Nikolaos Perakakis, Jannis Kountouras, Christos S. Mantzoros

Irisin is a myokine/adipokine induced by the exercise in mice and humans, which is proposed to induce "browning" of white adipose tissue, its primary target, thus increasing thermogenesis and energy expenditure. Since its identification, irisin has been linked to favorable effects on metabolic diseases, including obesity, type 2 diabetes mellitus (T2DM), lipid metabolism and cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and metabolic bone diseases. Generally, despite the promising profile of irisin in rodents, its effects on human are less recognized. Most, but not all studies show a positive association between irisin and indices of adiposity. In T2DM, NAFLD, and CVD, most observational studies reported lower irisin levels in patients than controls. Regarding metabolic bone diseases, irisin is positively associated with bone mineral density and strength in athletes, and inversely associated with osteoporotic fractures in postmenopausal osteoporosis. In PCOS, data remain largely conflicting. Irisin does not seem to be further reduced when two metabolic diseases, e.g., T2DM and NAFLD, or obesity and NAFLD exist though more data are needed. Furthermore, it seems that diverse confounders may have affected the results of different clinical studies. Irisin remains an appealing molecule from a pathophysiological point of view and an appealing therapeutic target for metabolic diseases, albeit much research is still needed.