title: Nesfatin-1 regulates the lateral hypothalamic area melanin-concentrating hormone-responsive gastric distension-sensitive neurons and gastric function via arcuate nucleus innervation.
abstract: 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.
authors.affiliation: Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, China. Electronic address: xu.luo@163.com.
authors.forename: Luo
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Jimo People's Hospital, Qingdao, Shandong, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Otolaryngology, Qingdao Municipal Hospital (Group), Qingdao, Shandong, China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Pang
authors.affiliation: Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Gao
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001111:Arcuate Nucleus of Hypothalamus / Q000503:physiopathology*; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004558:Electric Stimulation; D013271:Gastric Dilatation / Q000378:metabolism* / Q000503:physiopathology; D005769:Gastrointestinal Motility; D007026:Hypothalamic Area, Lateral / Q000378:metabolism* / Q000503:physiopathology; D007028:Hypothalamic Hormones / Q000494:pharmacology*; D008297:Male; D008543:Melanins / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons; D000080866:Nucleobindins; D009842:Oligopeptides / Q000494:pharmacology; D010907:Pituitary Hormones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000294:innervation
chemical_list: C527780:Ac-Arg-(Cys-Met-Ava-Arg-Val-Tyr-Ava-Cys)-NH2; D019138:Antibodies, Blocking; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D007028:Hypothalamic Hormones; D008543:Melanins; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D009842:Oligopeptides; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone
keywords: Gastric distension neurons; Gastric secretion; Lateral hypothalamic area; Melanin-concentrating hormone; Nesfatin-1