An animal study showed that even if the endothelial NO synthase-derived NO production is impaired or absent, leptin can induce neuronal NO synthase in the endothelium to maintain endothelium dependent-vasorelaxation in a mouse model of obesity with hyperleptineima or angiotensin-II-induced vascular dysfunction [43]. The gene discussed is AGT; the disease is obesity due to melanocortin 4 receptor deficiency.