Endogenous Glucagon-like Peptide-1 Suppresses High-Fat Food Intake by Reducing Synaptic Drive onto Mesolimbic Dopamine Neurons.
Endogenous Glucagon-like Peptide-1 Suppresses High-Fat Food Intake by Reducing Synaptic Drive onto Mesolimbic Dopamine Neurons.
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DOI：
10.1016/j.celrep.2015.06.062
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发表时间：
2015-08-04
期刊：
影响因子：
8.8
通讯作者：
Pang ZP
中科院分区：
文献类型：
--
作者：
Wang XF;Liu JJ;Xia J;Liu J;Mirabella V;Pang ZP
胰高血糖素样肽-1 (GLP-1) 及其类似物可作为食欲抑制剂，并已被证明在临床上可有效减轻肥胖个体的体重。中枢 GLP-1 在位于孤束核 (NTS) 的一小群脑干细胞中表达，该细胞投射到广泛的大脑区域。然而，目前尚不清楚大脑中释放的内源性 GLP-1 如何促进食欲调节。通过使用化学遗传学工具，我们发现中枢GLP-1作用于中脑腹侧被盖区（VTA）并抑制高脂肪食物的摄入。我们使用综合通路追踪和突触生理学来进一步证明 GLP-1 受体的激活会特异性降低 VTA 内投射到伏隔核 (NAc) 内壳的多巴胺 (DA) 神经元的兴奋性突触强度。这些数据表明，NTS 神经元释放的 GLP-1 可以通过抑制中脑边缘 DA 信号传导来减少高度适口的食物摄入。
Glucagon-like peptide-1 (GLP-1) and its analogs act as appetite suppressants and have been proven to be clinically efficacious in reducing body weight in obese individuals. Central GLP-1 is expressed in a small population of brainstem cells located in the nucleus tractus solitarius (NTS), which project to a wide range of brain areas. However, it remains unclear how endogenous GLP-1 released in the brain contributes to appetite regulation. By using chemogenetic tools, we discovered that central GLP-1 acts on the midbrain ventral tegmental area (VTA) and suppresses high-fat food intake. We used integrated pathway tracing and synaptic physiology to further demonstrate that activation of GLP-1 receptors specifically reduces the excitatory synaptic strength of dopamine (DA) neurons within the VTA that project to the nucleus accumbens (NAc) medial shell. These data suggest that GLP-1 released from NTS neurons can reduce highly palatable food intake by suppressing mesolimbic DA signaling.