Loss of either peripheral leptin production or central LepRb expression promotes overeating, decreases energy output and leads to severe obesity in rodents (Halaas et al., 1995; Pelleymounter et al., 1995; Chua et al., 1996) and humans (Montague et al., 1997; Farooqi et al., 1999), revealing the crucial role of this periphery/brain regulatory system. The gene discussed is LEP; the disease is Obesity.