Our previously published data show a synergistic effect between nPE1 and nPE2 enhancers such that the deletion of both produces a morbidly obese mouse [13]; when both neural enhancers are deleted, there is a precipitous drop in Pomc expression, to approximately 10% of WT levels that results in decreased energy expenditure, hyperphagia, and early-onset obesity. Here, POMC is linked to obesity due to melanocortin 4 receptor deficiency.