While developmental compensation may partially conceal the role for LepRb in AgRP neurons following its early ablation (9, 11, 12), animals lacking LepRb from early developmental times (throughout the body or the hypothalamus) exhibit dramatic hyperphagic obesity despite any compensation for their lack of LepRb in AgRP neurons or elsewhere (13). This evidence concerns the gene AGRP and obesity due to melanocortin 4 receptor deficiency.