The underlying physiological mechanism is that overweight and obesity lead to an increased secretion of adipocytokine, sympathetic nervous system excitation, activation of the renin–angiotensin–aldosterone system, lipid or insulin abnormalities, and alterations in the leptin pathway, which further leads to decreased vascular compliance, increased cardiac output, or insulin resistance [40]. This evidence concerns the gene REN and obesity due to melanocortin 4 receptor deficiency.