Indeed, increased renal sodium reabsorption and consequent expanded plasma volume sustained by compression of the kidney by perirenal and intrarenal fat and systemic/renal SNS and renin–angiotensin–aldosterone system (RAAS) overactivation have been subsequently identified as major factors mediating the initiation of hypertension in obesity [5, 26]. Here, REN is linked to obesity due to melanocortin 4 receptor deficiency.