Obesity, T2DM and oxidative stress contribute to lower NO bioavailability due to decreased NO production and accelerated NO removal, as a result of the uncoupling of the NO synthase, NO scavenging with formation of peroxynitrite, and TNF-α/inflammation and hypoxia-associated alterations in NO metabolism [12]. The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.