Functional analysis reveals differential effects of glutamate and MCH neuropeptide in MCH neurons
Functional analysis reveals differential effects of glutamate and MCH neuropeptide in MCH neurons
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DOI：
10.1016/j.molmet.2018.05.001
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发表时间：
2018-07-01
影响因子：
8.1
通讯作者：
Friedman, Jeffrey M.
中科院分区：
文献类型：
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作者：
Schneeberger, Marc;Tan, Keith;Friedman, Jeffrey M.
目的：下丘脑外侧（LH）黑色素浓缩激素（Melanin-concentrating hormone， MCH）神经元调节食物摄入和体重、葡萄糖代谢并传递蔗糖的奖励值。在本报告中，我们着手建立MCH和传统神经递质在这些神经元中的各自作用。方法：采用Cre-dependent molecular profiling technology （vTRAP）对MCH神经元进行分析。MCHCre小鼠与Vglut2（fl/fl）小鼠或DTR（fl/fl）小鼠杂交，以确定谷氨酸在MCH神经元中的作用。我们评估了代谢参数，如身体成分、葡萄糖耐量或蔗糖偏好。结果：我们发现，LH中几乎所有的MCH神经元都是谷氨酸能神经元，谷氨酸转运蛋白（VGlut2）敲除导致MCH神经元的谷氨酸能信号丧失，导致体重减轻、低食和多动行为，同时改善葡萄糖耐量和蔗糖偏好丧失。这些影响与MCH神经元消融后所见的效果难以区分。这些发现与敲除MCH神经肽的小鼠形成对比，后者表现出正常的葡萄糖偏好，并没有改善葡萄糖耐量。结论：总的来说，这些数据表明绝大多数MCH神经元是谷氨酸能神经元，谷氨酸和MCH信号介导这些神经元部分重叠的功能，可能是通过激活部分重叠的突触后群体。因此，MCH神经元的多种功能作用是由谷氨酸和MCH信号的复合介导的。Elsevier GmbH出版。
Objectives: Melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) regulate food intake and body weight, glucose metabolism and convey the reward value of sucrose. In this report, we set out to establish the respective roles of MCH and conventional neurotransmitters in these neurons.Methods: MCH neurons were profiled using Cre-dependent molecular profiling technologies (vTRAP). MCHCre mice crossed to Vglut2(fl/fl)mice or to DTR(fl/fl)were used to identify the role of glutamate in MCH neurons. We assessed metabolic parameters such as body composition, glucose tolerance, or sucrose preference.Results: We found that nearly all MCH neurons in the LH are glutamatergic and that a loss of glutamatergic signaling from MCH neurons from a glutamate transporter (VGlut2) knockout leads to a reduced weight, hypophagia and hyperkinetic behavior with improved glucose tolerance and a loss of sucrose preference. These effects are indistinguishable from those seen after ablation of MCH neurons. These findings are in contrast to those seen in mice with a knockout of the MCH neuropeptide, which show normal glucose preference and do not have improved glucose tolerance.Conclusions: Overall, these data show that the vast majority of MCH neurons are glutamatergic, and that glutamate and MCH signaling mediate partially overlapping functions by these neurons, presumably by activating partially overlapping postsynaptic populations. The diverse functional effects of MCH neurons are thus mediated by a composite of glutamate and MCH signaling. Published by Elsevier GmbH.