Obesity-induced oxidative stress reduces the activation of eNOS, leading to decreased NO bioavailability, endothelial dysfunction, and vascular hypertrophy, which ultimately contribute to increased AS (73, 74), resulting in structural vascular changes, including alterations in elasticity, capacitance (75), and resistance that are associated with a higher incidence and mortality of CVD (76). Here, NOS3 is linked to obesity due to melanocortin 4 receptor deficiency.