Spitzweg C, Joba W, Heufelder A E
Klinikum Innenstadt, Ludwig-Maximilians-Universität München.
Med Klin (Munich). 1998 Aug 15;93(8):478-85. doi: 10.1007/BF03042597.
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.
肥胖基因(ob基因)的克隆及其基因产物瘦素的特性鉴定,促成了一种饱腹感因子的发现。该因子能将外周脂肪储备量的信息传递给中枢神经系统,并调节后续的进食行为,从而在体重调节中发挥核心作用。在ob基因克隆后不久,人们就在中枢神经系统以及各种外周器官中发现了瘦素结合受体。外周脂肪储备与中枢神经系统中的瘦素受体之间的反馈回路,似乎在正常体重调节中起着重要作用。与病因不明的人类瘦素抵抗相关的肥胖不同,现在已知几种动物模型相关的肥胖综合征是由反馈回路在不同点的中断所致。此外,瘦素可能在胰岛素抵抗和II型糖尿病的表现中起作用。自从发现瘦素以来,已经进行了大量研究,以评估肥胖发生和表现所涉及的分子机制和信号转导途径。从迄今为止产生的大量数据来看,能量平衡调节的新概念和控制人类肥胖的目标策略应该很快就会出现。