Lu Zengbing, Cui Dexuan, Liu Julia Yuen Hang, Jiang Bin, Ngan Man Piu, Sakata Ichiro, Takemi Shota, Sakai Takafumi, Lin Ge, Chan Sze Wa, Rudd John A
School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
School of Health Sciences, Caritas Institute of Higher Education, Hong Kong, Hong Kong SAR, China.
Front Pharmacol. 2022 Apr 6;13:858522. doi: 10.3389/fphar.2022.858522. eCollection 2022.
Nesfatin-1 is an anorectic peptide expressed in both peripheral tissues and brain areas involved in the regulation of feeding, emotion and emesis. The aim of the present study is to characterize the distribution of NUCB2/nesfatin-1 in and to investigate the actions of nesfatin-1 to affect gastrointestinal contractility, emesis, food and water intake, and locomotor activity. The deduced amino acid sequence of nesfatin-1 using cloning showed high homology with humans and rodents. NUCB2 mRNA was detected throughout the entire brain and in the gastrointestinal tract, including the stomach and gut. Western blot analysis and immunohistochemistry confirmed the expression of nesfatin-1 protein in these regions. The NUCB2 mRNA levels in the hypothalamus, hippocampus and brainstem were significantly decreased, whereas that in the striatum were increased after 24 h starvation compared to -fed animals ( < 0.05). In studies, nesfatin-1 (0.3-1,000 pM) failed to contract or relax the isolated gastric antrum and intestinal segments. In conscious, freely moving animals, intracerebroventricular administration of nesfatin-1 (1-50 pmol) induced emesis ( < 0.05) and suppressed 6-h cumulative food intake ( < 0.05), without affecting the latency to feeding. Nesfatin-1 (25 pmol, i.c.v.) decreased 24-h cumulative food and water intake by 28.3 and 35.4%, respectively ( < 0.01). No significant differences in locomotor activity were observed. In conclusion, NUCB2/nesfatin-1 might be a potent regulator of feeding and emesis in . Further studies are required to elucidate the mechanism of actions of this peptide as a mediator linking the brainstem NUCB2/nesfatin-1 to forebrain system.
Nesfatin-1是一种厌食肽，在外周组织以及参与进食、情绪和呕吐调节的脑区均有表达。本研究的目的是描述NUCB2/nesfatin-1的分布，并研究nesfatin-1对胃肠收缩性、呕吐、食物和水摄入以及运动活性的影响。通过克隆推导的nesfatin-1氨基酸序列显示与人和啮齿动物具有高度同源性。在整个大脑以及胃肠道（包括胃和肠道）中均检测到了NUCB2 mRNA。蛋白质印迹分析和免疫组织化学证实了nesfatin-1蛋白在这些区域的表达。与进食动物相比，饥饿24小时后，下丘脑、海马和脑干中的NUCB2 mRNA水平显著降低，而纹状体中的水平升高（P<0.05）。在离体研究中，nesfatin-1（0.3 - 1000 pM）未能使离体胃窦和肠段收缩或舒张。在清醒、自由活动的动物中，脑室内注射nesfatin-1（1 - 50 pmol）可诱发呕吐（P<0.05）并抑制6小时累积食物摄入量（P<0.05），但不影响进食潜伏期。脑室内注射nesfatin-1（25 pmol）可使24小时累积食物和水摄入量分别减少28.3%和35.4%（P<0.01）。未观察到运动活性有显著差异。总之，NUCB2/nesfatin-1可能是[具体物种未提及]进食和呕吐的有效调节因子。需要进一步研究以阐明该肽作为连接脑干NUCB2/nesfatin-1与前脑系统的介质的作用机制。
