To be lean or not to be lean. Is leptin the answer?

Leptin and the leptin receptor genes have been identified as the site of mutations in the peripheral adipocyte hormone pathway responsible for obesity in the ob/ob mouse (Zhang et al., 1994) and the db/db mouse (Chen et al., 1996). In obese humans, ob/ob like mutations in leptin are rare but confirm a role for leptin (Montague et al., 1997), and db/db like mutations in the leptin receptor have not been found (Considine et al., 1996a); however, the increased understanding of the molecular basis for obesity has generated tremendous interest among scientists and patients alike. The new knowledge could be the base for intelligent drugs for the treatment of obesity. Herein we will put in perspective a) the physiological background that led to the discovery of leptin, b) leptin biosynthesis, c) leptin action and d) the clinical issues related to leptin as a drug for the treatment of obesity.