The assimilation, storage, and disposition of nutrient energy constitute a complex homeostatic system central to the survival of both prokaryotic and eukaryotic organisms. In vertebrates, and especially among land dwelling mammalian species, the ability to store large quantities of energy-dense fuel in the form of adipose tissue triglyceride permits survival during prolonged periods of food deprivation. In order to maintain such fuel stores during times of dietary scarcity or surfeit, some balance between energy intake and expenditure must be achieved. Lesions of the hypothalamus alter body weight suggesting that this brain region regulates nutritional state. These and other studies led to the hypothesis that body weight was regulated by a feedback loop in which peripheral signals reported nutritional information to an integratory center in the brain. However, the identity of these nutrition signals proved elusive.