Phenotypically, mice with the Ay mutation are similar to MC4R knockout mice [29,30]. Ay mice are hyperphagic and develop obesity, insulin resistance [38], and fatty liver [39] with age, so, Ay mice may be used as a model of melanocortin obesity to investigate the pharmacological effects of FGF21. Here, FGF21 is linked to obesity due to melanocortin 4 receptor deficiency.