Identification of a neuropeptide in suppressing food intake in zebrafish

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.