Intact endothelial cells maintain normal physiological function of the vasculature, but obesity disrupts its integrity and dysfunction, thus becoming a high risk factor for cardiovascular disease, including endothelial nitric oxide synthase (eNOS), Sirtuin 1 (SIRT1), oxidative stress, autophagic mechanisms, and endoplasmic reticulum stress are involved in this process. Here, SIRT1 is linked to obesity due to melanocortin 4 receptor deficiency.