[Leptin--new knowledge on the pathogenesis of obesity]

Abstract

Cloning of the ob-gene and characterization of its gene product leptin has led to the identification of a satiety factor, which signals the amount of peripheral fat stores to the central nervous system and regulates further feeding behaviour, thus playing a central role in the regulation of body weight. Soon after cloning of the ob-gene, a leptin-binding receptor has been identified in the central nervous system as well as in various peripheral organs. A feedback loop between peripheral fat stores and leptin receptors in the central nervous system appears to play an important role in normal body weight regulation. In contrast to human obesity, which associated with leptin resistance of uncertain etiology, the obesity syndromes associated with several animal models are now known to result from the interruption of the feedback loop at different points. Moreover, leptin may play a role in manifestation of insulin resistance and type II diabetes. Since the identification of leptin, a vast number of studies have been conducted to assess the molecular mechanisms and signal transduction pathways that are involved in the development and manifestation of obesity. From the large body of data generated to date, novel concepts of the regulation of energy balance and target strategies to control human obesity should soon be forthcoming.