FNDC5 and obesity due to melanocortin 4 receptor deficiency: FNDC5 was simultaneously characterized in 2002 by two independent groups [9, 10], but it was ten years later when irisin attracted more interest because it was reported to act as a mediator of the beneficial effect of exercise [8], increasing metabolic uncoupling and caloric expenditure and promoting browning [8, 11, 12], resulting in an improvement of obesity and glucose homeostasis.