Role of lateral septum glucagon-like peptide 1 receptors in food intake.
Role of lateral septum glucagon-like peptide 1 receptors in food intake.
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DOI：
10.1152/ajpregu.00460.2015
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发表时间：
2016-07
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影响因子：
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通讯作者：
S. J. Terrill;Christine M. Jackson;H. Greene;N. Lilly;Calyn B Maske;S. Vallejo;Diana L. Williams
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文献类型：
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作者：
S. J. Terrill;Christine M. Jackson;H. Greene;N. Lilly;Calyn B Maske;S. Vallejo;Diana L. Williams
后脑胰高血糖素样肽1 （GLP-1）神经元投射到许多前脑区域，包括外侧隔（LS）。使用荧光标记的GLP-1受体（GLP-1R）激动剂Exendin 4 (Ex4)，我们证明了GLP-1受体在整个大鼠LS中的结合。我们检测了Ex4和GLP-1R拮抗剂Exendin (9-39) （Ex9）在剂量低于阈值时给药到侧脑室的喂养效应。与对照组相比，ls内的Ex4抑制了夜间食物和高脂肪饮食（HFD）的摄入，而Ex9增加了夜间食物和高脂肪饮食（HFD）的摄入。在2 h的试验中，intra-LS Ex9显著增加了0.25 M蔗糖和4%玉米油。Ex4可引起恶心，但ls内给药Ex4不会引起异食癖。此外，ls - Ex4对升高+迷宫中的焦虑样行为没有影响。我们研究了LS GLP-1R在食物动机中的作用，通过检查渐进式比例（PR）计划中对蔗糖的操作性反应，在有和没有营养预负荷的情况下最大化GLP-1神经元的激活。预负荷强烈抑制了PR反应，但阻断LS中间细分的GLP-1R不影响两种负荷条件下对蔗糖的动机。中间LS Ex9处理显著减弱了营养负荷对后续饲料摄取量的抑制作用。相比之下，阻断LS背侧分支GLP-1R会增加PR反应和过夜食物摄入量。综上所述，这些研究表明，LS中GLP-1R的内源性活性影响摄食，特别是dLS GLP-1R在动机中发挥作用。
Hindbrain glucagon-like peptide 1 (GLP-1) neurons project to numerous forebrain areas, including the lateral septum (LS). Using a fluorescently labeled GLP-1 receptor (GLP-1R) agonist, Exendin 4 (Ex4), we demonstrated GLP-1 receptor binding throughout the rat LS. We examined the feeding effects of Ex4 and the GLP-1R antagonist Exendin (9-39) (Ex9) at doses subthreshold for effect when delivered to the lateral ventricle. Intra-LS Ex4 suppressed overnight chow and high-fat diet (HFD) intake, and Ex9 increased chow and HFD intake relative to vehicle. During 2-h tests, intra-LS Ex9 significantly increased 0.25 M sucrose and 4% corn oil. Ex4 can cause nausea, but intra-LS administration of Ex4 did not induce pica. Furthermore, intra-LS Ex4 had no effect on anxiety-like behavior in the elevated plus maze. We investigated the role of LS GLP-1R in motivation for food by examining operant responding for sucrose on a progressive ratio (PR) schedule, with and without a nutrient preload to maximize GLP-1 neuron activation. The preload strongly suppressed PR responding, but blockade of GLP-1R in the intermediate subdivision of the LS did not affect motivation for sucrose under either load condition. The ability of the nutrient load to suppress subsequent chow intake was significantly attenuated by intermediate LS Ex9 treatment. By contrast, blockade of GLP-1R in the dorsal subdivision of the LS increased both PR responding and overnight chow intake. Together, these studies suggest that endogenous activity of GLP-1R in the LS influence feeding, and dLS GLP-1Rs, in particular, play a role in motivation.