Mice with defective signaling in the melanocortin pathway, including those that fail to express the hypothalamic melanocortin 4 receptor (MC4R) or its agonist alpha-melanocyte stimulating hormone (α-MSH), and those that over-express the MC4R antagonists agouti or agouti-related protein (AGRP or ART), all develop late onset obesity and insulin resistance [1]. The gene discussed is AGRP; the disease is obesity due to melanocortin 4 receptor deficiency.