Leptin: The Tale of an Obesity Gene

The discovery of a "fat-melting hormone" named leptin (Greek root, leptos, meaning thin) by Friedman raised the hopes of one-third of the U.S. population that there is a simple solution to cure their obesity (1). The dream of such a solution for a "complex disease" was brought closer to reality a few months later by evidence of leptin resistance in human obesity (2). The concept of leptin resistance has since been extended to other studies in humans (3-6) and to the animal models of obesity (7-14), except for the ob/ob mouse, in which mutations in the ob gene result in an absolute leptin deficiency (1).