Evidence that the caudal brainstem is a target for the inhibitory effect of leptin on food intake
Evidence that the caudal brainstem is a target for the inhibitory effect of leptin on food intake
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DOI：
10.1210/en.143.1.239
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发表时间：
2002-01-01
期刊：
影响因子：
4.8
通讯作者：
Baskin, DG
中科院分区：
文献类型：
--
作者：
Grill, HJ;Schwartz, MW;Baskin, DG
进行了三个实验，以调查的假设，瘦素的行动在尾侧脑干（CBS）有助于其摄入抑制作用。第一个实验评估瘦素受体mRNA的解剖分布在大鼠CBS使用灵敏的荧光原位杂交方法与特异性的长形式的瘦素受体（OB-Rb）的核糖体探针。Ob-Rb mRNA杂交信号检测到参与控制食物摄入的几个CBS核，包括迷走神经背侧复合体和臂旁核的神经元。一个强大的杂交信号也得到了一些其他结构，包括舌下神经，三叉神经，外侧网状，耳蜗核，蓝斑和下橄榄的神经元细胞体。荧光原位杂交显示的解剖配置文件是在良好的协议与特异性抗体Ob-Rb的免疫细胞化学分析。在第二个实验中，探索CBS Ob-Rb与摄食行为的相关性，大鼠被给予第四次脑室内（i. c. v.）连续三天在熄灯前30分钟注射瘦素（0.1、0.83或5.0 μ g; n = 9-11/组）或赋形剂两个较高剂量在注射后2、4和24小时显著减少食物摄入，并导致体重显著降低。第四次静脉注射给药的剂量-反应曲线与通过侧部静脉注射插管接受瘦素的各组大鼠的剂量-反应曲线没有区别。在最后一个实验中，将心室阈下剂量的瘦素（0.1 μ g）单侧微量注射到迷走神经背侧复合体中，在2、4和24小时抑制了摄食。结果表明，CBS包含的神经元是瘦素在能量稳态控制中的潜在直接靶点。
Three experiments were performed to investigate the hypothesis that leptin action within the caudal brain stem (CBS) contributes to its intake inhibitory effects. The first experiment evaluated the anatomical distribution of leptin receptor mRNA in rat CBS using a sensitive fluorescence in situ hybridization method with a riboprobe specific for the long form of the leptin receptor (Ob-Rb). An Ob-Rb mRNA hybridization signal was detected in neurons of several CBS nuclei involved in the control of food intake, including the dorsal vagal complex and parabrachial nucleus. A strong hybridization signal was also obtained from neuronal cell bodies of a number of other structures including the hypoglossal, trigeminal, lateral reticular, and cochlear nuclei; locus ceruleus; and inferior olive. The anatomical profile revealed by fluorescence in situ hybridization was in good agreement with immunocytochemical analysis with an antibody specific to Ob-Rb. In a second experiment, exploring the relevance of CBS Ob-Rb to feeding behavior, rats were given a fourth intracerebroventricular (i.c.v.) injection of leptin (0.1, 0.83, or 5.0 mug; n = 9-11/group) or vehicle 30 min before lights-out on three consecutive days The two higher doses reduced food intake significantly at 2,4, and 24 h after injection and caused significant reductions of body weight. The dose-response profiles for fourth i.c.v. administration were indistinguishable from those obtained from separate groups of rats that received leptin via a lateral i.c.v. cannula. In the last experiment, a ventricle-subthreshold dose of leptin (0.1 mug) microinjected unilaterally into the dorsal vagal complex suppressed food intake at 2,4, and 24 h. The results indicate that the CBS contains neurons that are potentially direct targets for the action of leptin in the control of energy homeostasis.