As discussed earlier, although leptin showed excellent results in reversing many metabolic (Friedman, 2016) and cognitive (Harvey, 2010) dysfunctions in rodent models, and in leptin deficient humans (Farooqi et al., 1999), clinical trials with recombinant leptin in subjects with common obesity consistently reported disappointing outcomes (Heymsfield et al., 1999; Chan et al., 2005; Lo et al., 2005; Zelissen et al., 2005). Here, LEP is linked to obesity due to melanocortin 4 receptor deficiency.