In humans, the relative long-term constancy of body weight, the difficulty of successfully sustaining intentional weight loss, and the metabolic and behavioral alterations that accompany weight change provide strong evidence that body fat is biologically regulated.¹ The amount of energy stored as fat affects growth, puberty, fertility, and thyroid function, which suggests that humoral signals reflecting adipose-tissue mass interact with many neuroendocrine systems.¹ In mice, the products of the ob and db genes are the main candidates for the ligand and receptor, respectively, for a fat-to-brain signaling system. Mice with the ob mutation (now designated Lepob) have a deficiency . . .