Obesity-induced changes in medial smooth muscle cells disrupt the physiological facilitatory action of insulin on the responsiveness to vasodilator stimuli, whereas the adventitia and perivascular fat appear to be a source of proinflammatory and vasoactive factors possibly contributing to the endothelial and smooth muscle cell dysfunction and to the pathogenesis of vascular disease as pointed out by Tesauro and coworkers [84, 85]. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.