FNDC5 and obesity due to melanocortin 4 receptor deficiency: Irisin is an exercise-induced myokine that originates from proteolytic cleavage of fibronectin type III domain–containing protein 5 (FNDC5), a transmembrane protein expressed in several tissues, including the skeletal muscle and brain.1,2 Irisin was initially reported to reprogramme adipocyte metabolism and control peripheral glucose homeostasis.3,4FNDC5 single nucleotide polymorphisms (SNPs) have been associated with obesity and metabolic syndrome in humans.5‐7