REN and obesity due to melanocortin 4 receptor deficiency: Although the pathogenesis of obesity-related hypertension, e.g. insulin resistance, sympathetic nervous system stimulation, renin-angiotensin-aldosterone system activation, increased secretion of leptin and other bioactive factors, were demonstrated in previous studies, the mechanisms underlying obesity-associated hypertension and other associated metabolic disease remain unclear and need more studies9,37.