The vagus nerve mediates the physiological but not pharmacological effects of PYY3-36 on food intake.
The vagus nerve mediates the physiological but not pharmacological effects of PYY3-36 on food intake.
复制标题
迷走神经介导 PYY3-36 对食物摄入的生理作用，但不介导药理作用。
DOI：
10.1016/j.molmet.2024.101895
复制
发表时间：
2024
影响因子：
8.1
通讯作者：
Alonso AM
中科院分区：
文献类型：
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作者：
Alonso AM
YY肽(PYY3-36)是一种餐后释放的胃肠激素，具有很强的减食作用，其作用机制尚不完全清楚。解开这个系统是如何从生理上调节食物摄入的，可能有助于释放它的治疗潜力，同时将有害的影响降到最低。在这里，我们证明了生理释放的PYY3-36的食欲抑制效应需要胚系和出生后靶向敲除迷走神经传入神经中的PYY3-36偏好受体(神经肽Y(NPY)Y2受体(Y2R))，而不是外周给药剂量。出生后Y2R基因的敲除导致了一过性体重表型，这在生殖系模型中并不明显。迷走神经Y2R信号的丢失也会导致与胃排空加速相关的进食模式改变。这些结果对基于PYY的减肥药的设计具有重要意义。
Peptide YY (PYY3-36) is a post-prandially released gut hormone with potent appetite-reducing activity, the mechanism of action of which is not fully understood. Unravelling how this system physiologically regulates food intake may help unlock its therapeutic potential, whilst minimising unwanted effects. Here we demonstrate that germline and post-natal targeted knockdown of the PYY3-36preferring receptor (neuropeptide Y (NPY) Y2 receptor (Y2R)) in the afferent vagus nerve is required for the appetite inhibitory effects of physiologically-released PYY3-36, but not peripherally administered pharmacological doses. Post-natal knockdown of the Y2R results in a transient body weight phenotype that is not evident in the germline model. Loss of vagal Y2R signalling also results in altered meal patterning associated with accelerated gastric emptying. These results are important for the design of PYY-based anti-obesity agents.