LEPTIN - NOVEL CONCEPTS OF THE PATHOPHYSIOLOGY OF OBESITY

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 regu lates further feeding behaviour, thus playing a central role in the re gulation of body weight. Soon after cloning of the ob-gene, a leptin-b inding receptor has been identified in the central nervous systems as well as in various peripheral organs. A feedback loop between peripher al fat stores and leptin receptors in the central nervous system appea rs to play an important role in normal body weight regulation. In cont rast to human obesity, which associated with leptin resistance of unce rtain etiology, the obesity syndromes associated with several animal m odels are now known to result from the interruption of the feedback lo op at different points. Moreover, leptin may play a role in manifestat ion of insulin resistance and type II diabetes. Since the identificati on of leptin, a vast number studies have been conducted to assess the molecular mechanisms and signal transduction pathways that are involve d 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 forth-coming.