Irisin: 'fat' or artefact

Soon after the discovery of the muscle-derived factor irisin, a great controversy arose in the literature regarding certain inconsistencies in the regulation of the fibronectin type III domain containing 5 protein (FNDC5/irisin) after exercise, as well as the unpredicted association of circulating irisin levels with parameters of adiposity in humans. Due to these questionable findings, doubts as to the identity of the soluble portion of FNDC5 as well as the real role of irisin and its possible therapeutic applications in the treatment of obesity and diabetes have proliferated. We recently postulated that FNDC5/irisin is an adipokine expressed and secreted by white adipose tissue in rats and humans. Its circulating concentration correlates with adiposity in humans among independent cohorts of patients. Further analysis, focused on obesity-related metabolic disorders, has shown that irisin could play a role in promoting insulin resistance or act as an adaptive response to counteract disturbances in glucose and lipid homoeostasis in obesity. Overall, this leads us to raise the question whether the new factor, increased in circulation of obese patients, is really irisin-reflecting fat mass or it is an artefact. Therefore, the current review is focused on the potential participation of adipose tissue in irisin circulating levels, and the role of irisin in metabolic pathologies associated with obesity in an attempt to clarify the controversy generated by these recently published reports.