Since its identification in 2012, irisin has been suggested to play a favorable role in the context of metabolic diseases, including obesity, type 2 diabetes mellitus (T2DM), lipid metabolism and cardiovascular disease, nonalcoholic fatty liver disease (NAFLD), polycystic ovary syndrome, and metabolic bone diseases9. Here, FNDC5 is linked to obesity due to melanocortin 4 receptor deficiency.