FNDC5 and obesity due to melanocortin 4 receptor deficiency: Boström et al. observed that muscle-specific overexpression of the peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) in mice induced a brown fat-like gene program.[13] Mice overexpressing PGC-1α are not only resistant to obesity but also prone to the formation of multilocular and UCP1-positive adipocytes.[14] Profiling of the muscle genes activated by PGC-1α revealed fibronectin type III domain containing 5 (FNDC5), which undergoes proteolytic cleavage to release irisin into the blood.