The protein product of the obese (ob) gene has been cloned and a 167 amino-acid hormone produced in adipose tissue discovered.12 This hormone, which acts on the hypothalamus to reduce food intake and increase energy expenditure, has been named leptin, from the Greek word for thin. Obese ob/ob mice have a mutation of the ob gene resulting in a lack of active leptin. Another type of obese and diabetic mice has a mutation of the diabetes (db) gene, which produces a defective leptin receptor.13 This leads to a compensatory increase in ob gene expression and in plasma leptin levels. Consequently, leptin administration has no effect on db/db mice, whereas it reverses obesity in ob/ob mice. Weight loss is entirely due to loss of fat mass.