The mechanisms involved in obesity-associated hypertension are complex and include [1] physical compression of the kidneys from excess fat in and around the kidneys, [2] sympathetic nervous system (SNS) overactivation, [3] activation of the renin–angiotensin–aldosterone system (RAAS), [4] dysregulation in adipose tissue-secreted cytokines, such as leptin, insulin, resistance, TNF-α, and IL-6, [5] systemic insulin resistance, [6] endothelial dysfunction, and [7] structural and functional renal changes. The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.