Preclinical studies have consistently demonstrated the multiple potent therapeutic benefits of FGF21 for a cluster of obesity-related cardiometabolic disorders, including the reduction in adiposity and improvement in insulin resistance, hyperglycemia, dyslipidemia, NAFLD, atherosclerosis, and heart dysfunction (Geng et al, 2020; Jin et al, 2023b). Here, FGF21 is linked to obesity due to melanocortin 4 receptor deficiency.