Obesity-associated insulin resistance promotes endothelial stiffness by increasing saltocorticoid receptors and activating endothelial Na+ channels, which allows impaired eNOS activation [2,3,4], dysfunctional adipose tissue near the vessel wall promotes vascular stiffness by secreting multiple vasoactive factors, and transforming growth factor and connective tissue growth factor promote extracellular matrix protein synthesis when stimulated by obesity conditions [5]. Here, CCN2 is linked to obesity due to melanocortin 4 receptor deficiency.