Attenuation of lipopolysaccharide anorexia by antagonism of caudal brain stem but not forebrain GLP-1-R
Attenuation of lipopolysaccharide anorexia by antagonism of caudal brain stem but not forebrain GLP-1-R
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DOI：
10.1152/ajpregu.00163.2004
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发表时间：
2004-11-01
影响因子：
2.8
通讯作者：
Kaplan, JM
中科院分区：
文献类型：
--
作者：
Grill, HJ;Carmody, JS;Kaplan, JM
中枢胰高血糖素样肽-1（GLP-1）系统与摄食行为的控制有关。在这里，我们探讨GLP-1介导的神经元对全身性LPS给药的反应，并解决尾脑干和前脑GLP-1受体（GLP-1-R）的介导的反应的相对重要性。第四次脑室内递送GLP-1-R拮抗剂毒蜥外泌肽（9 - 39）（10 μ g）本身在注射后24小时内不影响食物摄入，但显著减弱LPS（100 μ g/kg）处理后获得的食物摄入的其他稳健（类似于60%）减少。这一结果强调了尾侧脑干GLP-1-R在LPS厌食症介导中的作用，但不排除前脑受体也参与反应的可能性。通过将GLP-1-R拮抗剂输送至第三脑室，并通过闭塞脑导水管阻断脑脊液尾侧流，解决前脑贡献。因此，毒蜥外泌肽-（9 - 39）递送仅限于前脑，并不减弱对LPS的脑保护反应。这些数据表明，LPS厌食症是介导的，在一定程度上，通过释放的天然肽作用于GLP-1-R的尾侧脑干。
The central glucagon-like peptide-1 (GLP-1) system has been implicated in the control of feeding behavior. Here we explore GLP-1 mediation of the anorexic response to administration of systemic LPS and address the relative importance of caudal brain stem and forebrain GLP-1 receptor (GLP-1-R) for the mediation of the response. Fourth-intracerebroventricular delivery of the GLP-1-R antagonist exendin( 9 - 39) ( 10 mug) did not itself affect food intake in the 24 h after injection but significantly attenuated the otherwise robust ( similar to 60%) reduction in food intake obtained after LPS ( 100 mug/kg) treatment. This result highlights a role for caudal brain stem GLP-1-R in the mediation of LPS anorexia but does not rule out the possibility that forebrain receptors also contribute to the response. Forebrain contribution was addressed by delivery of the GLP-1-R antagonist to the third ventricle with the caudal flow of cerebrospinal fluid blocked by occlusion of the cerebral aqueduct. Exendin-(9 - 39) delivery thus limited to forebrain did not attenuate the anorexic response to LPS. These data suggest that LPS anorexia is mediated, in part, by release of the native peptide acting on GLP-1-R within the caudal brain stem.