Obesity-related hypertension is initiated by increased renal sodium reabsorption and plasma volume expansion due to renal compression by perirenal/sinus fat and moderate increases in systemic/renal SNS and RAAS activity sustained by a complex interplay among hyperleptinemia, AngII, intermedin, adrenomedullin, and impaired baroreceptor and chemoreceptor reflexes. The gene discussed is ADM; the disease is obesity due to melanocortin 4 receptor deficiency.