Chronic central administration of ghrelin reverses the effects of leptin

Chronic central administration of ghrelin reverses the effects of leptin
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DOI:
10.1038/sj.ijo.0802647
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发表时间:
2004-10-01
影响因子:
4.9
通讯作者:
Lee, KU
Lee, KU
中科院分区:
医学2区
文献类型:
--
作者:
Kim, MS;Namkoong, C;Lee, KU

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目的:确定慢性中央给药胃饥饿素(ghrelin)是否能阻断瘦素对食物摄入、肥胖、血浆代谢参数和激素浓度的影响。设计:大鼠脑室内(ICV)输注瘦素(5mg /天)7天,加或不加胃促生长素(1.2杯/天)。给予瘦素和胃饥饿素的大鼠分为自由喂养组和食物限制组。测量方法:每天监测体重和食物摄入量。第8天处死后,测定附睾脂肪重量和空腹血浆葡萄糖、胰岛素、瘦素、胃促生长素、IGF-1和脂联素浓度。结果:ICV输注瘦素可减少39%的食物摄入量和41%的脂肪重量。瘦素降低了血浆中葡萄糖、胰岛素和瘦素的浓度,增加了血浆胃饥饿素的水平。ghrelin的中央联合用药阻断了瘦素的作用。胃饥饿素的大部分作用因食物限制而减弱,但在食物限制的大鼠中,胃饥饿素对肥胖和血浆胰岛素浓度的作用仍然存在。结论:胃饥饿素主要通过改变食物摄取量来逆转瘦素的作用,但胃饥饿素可能对肥胖和血浆胰岛素水平具有独立于摄食效应的调节作用。
OBJECTIVE: To determine whether chronic central administration of ghrelin can block the effects of leptin on food intake, adiposity, and plasma concentrations of metabolic parameters and hormones.DESIGN: Intracerebroventricular (ICV) infusions of leptin (5 mg/day) for 7 days, with or without ghrelin (1.2 mug/day), in rats. Rats administered leptin plus ghrelin were divided into ad lib-fed and food-restricted groups.MEASUREMENT: Body weight and food intake were monitored daily. Following killing on day 8, epididymal fat weight and fasting plasma concentrations of glucose, insulin, leptin, ghrelin, IGF-1, and adiponectin were determined.RESULTS: ICV infusion of leptin decreased food intake by 39% and fat weight by 41%. Leptin decreased plasma concentrations of glucose, insulin, and leptin and increased plasma ghrelin levels. Central coadministration of ghrelin blocked the effects of leptin. Most of the effects of ghrelin were diminished by food restriction but ghrelin effect on adiposity and plasma insulin concentrations remained in food-restricted rats.CONCLUSION: Chronic central administration of ghrelin reversed the effects of leptin, primarily by altering food intake, but ghrelin may have regulatory effects on adiposity and plasma insulin levels independent of feeding effect.