METHODS AND COMPOSITIONS FOR MODULATING LEPTIN ACTIVITY

摘要

Administration of leptin affects food intake and body weight in animals and humans by a mechanism involving actions on specific regions of the hypothalamus. CIS-1, SOCS-1, SOCS-2 and SOCS-3 genes were investigated for their ability to antagonize leptin action. In mammalian cell lines, SOCS-3 completely blocked leptin induced signal-transduction, whereas CIS, SOCS-1 and SOC-2 were without effect. SOCS-3 is a major target of leptin action in leptin responsive cells in the hypothalamus, and SOCS-3 is a potent inhibitor of leptin signaling. Increased SOCS-3 activity in leptin-responsive neurons is a potential mechanism for the leptin resistance observed in syndromes of obesity, affective mood disorders and reproductive disorders.