The role of the vagal nerve in peripheral PYY3-36-induced feeding reduction in rats
The role of the vagal nerve in peripheral PYY3-36-induced feeding reduction in rats
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DOI：
10.1210/en.2004-1266
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发表时间：
2005-05-01
期刊：
影响因子：
4.8
通讯作者：
Nakazato, M
中科院分区：
文献类型：
--
作者：
Koda, S;Date, Y;Nakazato, M
肽 YY (PYY) 是一种食欲肽，餐后从远端胃肠道分泌。 PYY3-36 是循环 PYY 的主要形式，以高亲和力与下丘脑神经肽 Y Y2 受体 (Y2-R) 结合，减少啮齿动物和人类的食物摄入量。参与进食的其他胃肠道激素，包括胆囊收缩素、胰高血糖素样肽 1 和生长素释放肽，通过迷走神经传入神经和/或血流将饱腹感或饥饿信号传递到大脑。在这里，我们确定了传入迷走神经在 PYY 功能中的作用。腹部迷走神经切断术消除了 PYY3-36 对大鼠的厌食作用。 PYY3-36 的外周给药可诱导假手术大鼠弓状核中 Fos 的表达，但不会诱导迷走神经切断大鼠的弓状核表达。我们发现 Y2-R 在大鼠结状神经节中合成并转运至迷走神经传入末梢。静脉注射时，PYY3-36 会刺激胃迷走神经传入神经的放电。考虑到Y2-R存在于迷走神经传入纤维中，PYY3-36可以通过Y2-R直接改变迷走神经传入神经的放电率。我们还研究了来自孤束核的上行纤维对 PYY3-36 介导的饱腹感信号传输的影响。在大鼠中，孤束核嘴侧的双侧中脑横断也消除了 PYY3-36 诱导的进食减少。这项研究表明外周 PYY3-36 可能部分通过迷走神经传入途径将饱腹感信号传递到大脑。
Peptide YY (PYY), an anorectic peptide, is secreted postprandially from the distal gastrointestinal tract. PYY3-36, the major form of circulating PYY, binds to the hypothalamic neuropeptide Y Y2 receptor (Y2-R) with a high-affinity, reducing food intake in rodents and humans. Additional gastrointestinal hormones involved in feeding, including cholecystokinin, glucagon-like peptide 1, and ghrelin, transmit satiety or hunger signals to the brain via the vagal afferent nerve and/or the blood stream. Here we determined the role of the afferent vagus nerve in PYY function. Abdominal vagotomy abolished the anorectic effect of PYY3-36 in rats. Peripheral administration of PYY3-36 induced Fos expression in the arcuate nucleus of sham-operated rats but not vagotomized rats. We showed that Y2-R is synthesized in the rat nodose ganglion and transported to the vagal afferent terminals. PYY3-36 stimulated firing of the gastric vagal afferent nerve when administered iv. Considering that Y2-R is present in the vagal afferent fibers, PYY3-36 could directly alter the firing rate of the vagal afferent nerve via Y2-R. We also investigated the effect of ascending fibers from the nucleus of the solitary tract on the transmission of PYY3-36-mediated satiety signals. In rats, bilateral midbrain transections rostral to the nucleus of the solitary tract also abolished PYY3-36-induced reductions in feeding. This study indicates that peripheral PYY3-36 may transmit satiety signals to the brain in part via the vagal afferent pathway.