Mutations on MC4R has been shown to induce obesity in rodents and humans (Huszar et al., 1997; Vaisse et al., 1998; Tallam et al., 2005), and its activation hyperpolarizes parasympathetic preganglionic neurons in brainstem via PKA-dependent activation of tolbutamide-sensitive KATP channels and depolarize the sympathetic ones, which could be one of the factors responsible to inducing obesity-associated hypertension. Here, MC4R is linked to obesity due to melanocortin 4 receptor deficiency.