In seminal studies in mice, Ahima et al. (6) showed that, as well as being a marker of fat mass, leptin acts as a signal of nutrient availability; acute caloric restriction (CR)/starvation (without loss of fat mass) leads to a rapid fall in circulating leptin concentration, hyperphagia, reduced energy expenditure, and hypogonadism (6), features that mimic genetic leptin deficiency in rodents and humans (7, 8) and can be normalized by leptin administration (6, 9). The gene discussed is LEP; the disease is hypogonadism.