Biological stress during gestation, triggered by a variety of nutritional, inflammatory, vascular, behavioral, or psychosocial perturbations, can promote obesity in the offspring by reorganizing central neural pathways through the programming of energy balance ‘set points’, in particular by involving the hypothalamic–pituitary–adrenal stress axis, which interacts with brain circuits controlling energy balance; furthermore, cortisol increases leptin secretion and limits CNS leptin-induced efferents [158]. The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.