Xu Luo, Wang Hongbo, Gong Yanling, Pang Mingjie, Sun Xiangrong, Guo Feifei, Gao Shengli
Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, China.
Department of Gastroenterology, Jimo People's Hospital, Qingdao, Shandong, China.
Metabolism. 2017 Feb;67:14-25. doi: 10.1016/j.metabol.2016.10.010. Epub 2016 Oct 28.
Nesfatin-1, a recently discovered neuropeptide involved in satiety. Recent studies have revealed that central nesfatin-1 inhibits gastric emptying and gastric acid secretion, though the mechanisms involved in these processes are not known. We aim to explore the effects of nesfatin-1 on a population of gastric distension (GD)-sensitive neurons in the lateral hypothalamus (LHA), gastric motility, and gastric secretion and the role for an arcuate nucleus (Arc)-LHA neural pathway in these processes. Single unit extracellular discharge recordings were made in of LHA. Further, gastric motility and gastric secretion in rats were monitored. Retrograde tracing and fluorescent immunohistochemical staining were used to explore nesfatin-1 neuron projection. The results revealed that administration of nesfatin-1 to the LHA or electric stimulation of the Arc could alter the neuronal activity of melanin-concentrating hormone (MCH)-responsive, GD-responsive neurons in LHA, which could be blocked by pretreatment with MCH receptor-1 antagonist PMC-3881-PI or weakened by pretreatment of a nesfatin-1 antibody in LHA. Administration of nesfatin-1 into LHA could inhibit gastric motility and gastric secretion, and these effects could be enhanced by administration of PMC-3881-PI. Electrical stimulation of Arc promoted the gastric motility and gastric secretion. Nesfatin-1 antibody or PMC-3881-PI pretreatment to LHA had no effect on Arc stimulation-induced gastric motility, but these pretreatments did alter Arc stimulation-induced effects on gastric secretion. Our findings suggest that nesfatin-1 signaling in LHA participates in the regulation of efferent information from the gastrointestinal tract and gastric secretion which also involve MCH signaling. Further, they show that a nesfatin-1-positive Arc to LHA pathway is critical for these effects.
Nesfatin-1是一种最近发现的参与饱腹感调节的神经肽。近期研究表明，中枢Nesfatin-1可抑制胃排空和胃酸分泌，但其相关机制尚不清楚。我们旨在探究Nesfatin-1对下丘脑外侧区（LHA）中一群对胃扩张（GD）敏感的神经元、胃动力和胃分泌的影响，以及弓状核（Arc）-LHA神经通路在这些过程中的作用。对LHA进行单单位细胞外放电记录。此外，监测大鼠的胃动力和胃分泌情况。采用逆行追踪和荧光免疫组织化学染色来探究Nesfatin-1神经元投射。结果显示，向LHA注射Nesfatin-1或电刺激Arc可改变LHA中对黑色素浓缩激素（MCH）有反应、对GD有反应的神经元的活动，而这种改变可被MCH受体-1拮抗剂PMC-3881-PI预处理阻断，或因在LHA中预先注射Nesfatin-1抗体而减弱。向LHA注射Nesfatin-1可抑制胃动力和胃分泌，而注射PMC-3881-PI可增强这些作用。电刺激Arc可促进胃动力和胃分泌。对LHA进行Nesfatin-1抗体或PMC-3881-PI预处理对Arc刺激诱导的胃动力没有影响，但这些预处理确实改变了Arc刺激对胃分泌的影响。我们的研究结果表明，LHA中的Nesfatin-1信号参与了来自胃肠道的传出信息调节和胃分泌调节，这一过程也涉及MCH信号。此外，研究结果表明，Nesfatin-1阳性的从Arc到LHA的通路对这些作用至关重要。
