Centrally, disruption of insulin receptors in the hypothalamus causes obesity, insulin resistance, hyperphagia, and hyperleptinemia in mice (32) and when insulin was injected into the cerebral ventricles of baboons in a study over 40 years ago, food intake and endogenous glucose production were both suppressed (9) underpinning the central role of insulin in energy homeostasis. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.