Orexin-A injected into various brain sites increases feeding [8], spontaneous physical activity (SPA) and thermogenesis [9,10,11,12,13,14] and orexin neuron ablation is associated with late-onset obesity and reduced locomotion, despite hypophagia [15,16,17,18]. Here, HCRT is linked to obesity due to melanocortin 4 receptor deficiency.