In both humans and rodents, obesity is associated with blunted β-AR-mediated lipolysis and lipid oxidation in adipose tissue (Reynisdottir et al., 1994; Arner, 1999; Jocken et al., 2008), but the mechanisms linking nutrient overload to catecholamine resistance remain poorly understood. Here, ADRB2 is linked to obesity due to melanocortin 4 receptor deficiency.