Ghrelin may also improve endothelial function mimicking phosphoinositol 3-kinase-dependent actions of insulin to stimulate production of NO by endothelial cells and restoring the endothelin 1/nitric oxide balance in patients with obesity-related MetS, as observed by Tesauro and coworkers [142–144]. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.