Interestingly, recent studies have shown that muscle exercise can promote the secretion of anti-inflammatory myokines, such as interleukin (IL)-6, IL-15, myostatin, irisin, and myonectin, able to contrast the pro-inflammatory state induced by overweight and obesity and the proper of insulin resistance (IR) [8,9,10]. Here, FNDC5 is linked to obesity due to melanocortin 4 receptor deficiency.