title: Nesfatin-1 signaling in the basom edial amygdala modulates the gastric distension-sensitive neurons discharge and decreases gastric motility via melanocortin 3/4 receptors and modified by the arcuate nucleus.
abstract: Nesfatin-1 is a novel anorexigenic peptide that regulates feeding behavior and gastrointestinal function. This study aimed to explore the effects of nesfatin-1 on gastric distension (GD)-sensitive neurons in the basomedial amygdala (BMA) and the potential mechanism for nesfatin-1 to regulate gastric motility through the arcuate nucleus (Arc). The projection of nerve fiber and expression of nesfatin-1 were observed by retrograde tracing and fluo-immunohistochemistry staining. Single-unit discharges in the BMA were recorded extracellularly, and gastric motility in conscious rats was monitored. Results showed that the nesfatin-1/ fluorogold-double labeled neurons were observed in the Arc. Nesfatin-1 could excite the GD-excitatory neurons and inhibit the GD-inhibitory neurons in the BMA. Gastric motility and gastric emptying were significantly reduced by nesfatin-1 administration to the BMA in a dose-dependent manner. The effects of nesfatin-1 could be partially blocked by melanocortin 3/4 receptors antagonist, SHU9119. Electrical stimulation of the Arc significantly excited the response of GD neurons to nesfatin-1 and promoted gastric motility. Nevertheless, these effects could be mitigated by pretreatment with anti-NUCB2/nesfatin-1 antibody. It is suggested that nesfatin-1 in the BMA plays an important role in decreasing gastric motility and the Arc may be involved in this regulation process.
authors.affiliation: Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, PR China. Electronic address: xu.luo@163.com.
authors.forename: Luo
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, PR China.
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, PR China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Guo
authors.affiliation: Otolaryngological department, Qingdao Municipal Hospital (Group), Qingdao, Shandong, PR China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Pang
authors.affiliation: Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, PR China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, PR China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, PR China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Gong
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005746:Gastric Emptying / Q000502:physiology; D005769:Gastrointestinal Motility / Q000502:physiology*; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D000080866:Nucleobindins; D017208:Rats, Wistar; D044104:Receptor, Melanocortin, Type 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D013272:Stomach Diseases / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; C103272:SHU 9119; D009074:Melanocyte-Stimulating Hormones
keywords: Amygdala; Arcuate nucleus; Gastric distension responsive neurons; Gastric motility; Nesfatin-1