INS and obesity due to melanocortin 4 receptor deficiency: Adipose tissue changes dramatically in obesity and can effectively influence endothelial function through multiple underlying mechanisms including high production of mediators that can impair insulin action in the skeletal muscle like free fatty acids; decreasing adiponectin production, which is associated with improving insulin sensitivity; and producing high amounts of compounds with the ability to affect endothelial function like adipokines that can directly affect vascular homeostasis.33