We aimed at investigating whether FGF21 affects metabolism inmale and female mice with the lethal yellow (Ay) mutation, which results in MC4R blockage and obesity development.Obese C57Bl-Ay male and female mice were administered subcutaneously for 10 days with vehicle or FGF21 (1 mg per1 kg). This evidence concerns the gene FGF21 and obesity due to melanocortin 4 receptor deficiency.