REN and obesity due to melanocortin 4 receptor deficiency: According to D’Elia et al. overweight or obesity and accompanying insulin resistance could mediate the development of isolated systolic hypertension through the increase in the renin-angiotensin-aldosterone system activity, in the sympathetic tone and salt-sensitivity, all in turn leading to endothelial dysfunction, arterial stiffness and increase in blood pressure [17].