The reason that our LepRb-POMC mice do not develop obesity on a LFD (Fig. 6) or chow diet [16], in contrast to the CA STAT3-POMC mice, may be explained by the lack of elevated leptin levels; i.e. despite the forced increase of LepRb, the circulating leptin concentration is not sufficient to activate STAT3 and to increase Socs3 expression to the threshold-level that causes long-term cellular leptin-resistance. The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.