LEP and obesity due to melanocortin 4 receptor deficiency: Leptin is an adipocyte-derived hormone encoded by the ob gene.115, 116 About two decades ago, the discovery that a genetic mutation in the ob gene caused leptin deficiency and severe obesity showed that leptin is a critical molecule in the regulation of energy expenditure, food intake and attenuation of adipose mass.115, 116 It was demonstrated that leptin has a high binding affinity in the hypothalamus, and it inhibited the orexigenic hormone NPY gene expression and synthesis.118