The purpose of Part 1 of this review is to summarize the available data on recently emerging mechanisms believed to contribute to obesity-related hypertension through increased sodium reabsorption and volume expansion, such as: physical compression of the kidney by perirenal/intrarenal fat and overactivation of the systemic/renal SNS and the renin–angiotensin–aldosterone system. The gene discussed is REN; the disease is obesity due to melanocortin 4 receptor deficiency.