Obesity-induced metabolic and vascular dysfunction, including chronic gut and adipose tissue inflammation, insulin and leptin resistance, and arterial hypertension, as well as dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, have emerged as the key pathophysiological mechanisms for the development of depression and anxiety in individuals with obesity. The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.