A recent study has also shown that lack of either of the orexin receptors diminishes weight gain in a DIO paradigm60; consistent with this, we found that an Hcrtr antagonist delivered i.c.v. showed a greater effect on weight than did i.c.v. infusion of calcitonin, suggesting that an orally available agent that crossed the blood–brain barrier could have a potentially beneficial effect for the management of obesity. This evidence concerns the gene CALCA and obesity disorder.