State Key Laboratory of Biocontrol and School of Life Sciences, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), and Guangdong Provincial Key Laboratory for Aquatic Economic Animals, Sun Yat-Sen University, Guangzhou, 510275, China.
State Key Laboratory of Biocontrol and School of Life Sciences, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), and Guangdong Provincial Key Laboratory for Aquatic Economic Animals, Sun Yat-Sen University, Guangzhou, 510275, China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266373, China.
Biochem Biophys Res Commun. 2024 Nov 19;734:150752. doi: 10.1016/j.bbrc.2024.150752. Epub 2024 Sep 26.
Neuropeptides play crucial roles in regulating various physiological processes in vertebrates. In this study, we identified a novel neuropeptide-encoding gene, nwk, in the genomes of some vertebrate species. The nwk cDNA was subsequently cloned from the brain of zebrafish. The Nwk precursor comprises 88 amino acids, with a putative mature peptide (Nwk-22) of 22 amino acids. Sequence analysis revealed that Nwk-22 is relatively conserved across vertebrate species. Nwk is predominantly expressed in the brain, with positive mRNA cells identified in the TPp and preoptic area. Intraperitoneal injection of Nwk-22 suppressed food intake and downregulated the mRNA expression of the orexigenic factor agouti-related peptide (agrp) in zebrafish. Additionally, a CRISPR/Cas9 approach was used to generate nwk mutant zebrafish. The nwk zebrafish exhibited increased food consumption compared to wild-type controls. Furthermore, Nwk-22a injection in nwk fish also suppressed agrp expression while stimulating the expression of the anorexigenic gene pomca, further supporting the anorexigenic role of Nwk. Taken together, these findings suggest that Nwk functions as an anorexigenic factor, reducing food intake by downregulating orexigenic genes like agrp and upregulating anorexigenic genes like pomc in zebrafish.
神经肽在调节脊椎动物的各种生理过程中起着至关重要的作用。在这项研究中，我们在一些脊椎动物的基因组中鉴定出了一种新的神经肽编码基因 nwk。随后，我们从斑马鱼的大脑中克隆了 nwk cDNA。Nwk 前体由 88 个氨基酸组成，具有 22 个氨基酸的推定成熟肽（Nwk-22）。序列分析表明，Nwk-22 在脊椎动物中相对保守。Nwk 主要在大脑中表达，在 TPp 和视前区有阳性 mRNA 细胞。Nwk-22 的腹腔注射抑制了斑马鱼的摄食，并下调了食欲刺激因子 agouti 相关肽（agrp）的 mRNA 表达。此外，我们还使用 CRISPR/Cas9 方法生成了 nwk 突变斑马鱼。与野生型对照相比，nwk 斑马鱼的食物摄入量增加。此外，Nwk-22a 注射到 nwk 鱼中也抑制了 agrp 的表达，同时刺激了厌食基因 pomca 的表达，进一步支持了 Nwk 的厌食作用。综上所述，这些发现表明 Nwk 作为一种厌食因子发挥作用，通过下调 agrp 等食欲刺激基因和上调 pomc 等厌食基因来减少斑马鱼的食物摄入。
