Nesfatin-1-like peptide is a negative regulator of cardiovascular functions in zebrafish and goldfish

Nucleobindins (NUCB1 and NUCB2) were originally identified as calcium and DNA binding proteins. Nesfatin-1 (NEFA/nucleobindin-2-Encoded Satiety and Fat-Influencing proteiN-1) is an 82 amino acid anorexigenic peptide encoded in the N-terminal region of NUCB2. We have shown that nesfatin-1 is a cardiosuppressor in zebrafish. Both NUCB1 and NUCB2 possess a -very highly conserved bioactive core. It was found that a nesfatin-1-like peptide (NLP) encoded in NUCB1 suppresses food intake in fish. In this research, we investigated whether NLP has nesfatin-1-like effects on cardiovascular functions. NUCB1/NLP-like immunoreactivity was found in the atrium and ventricle of the heart and skeletal muscle of zebrafish. Intraperitoneal injection (IP) of either zebrafish NLP or rat NLP suppressed cardiac functions in both zebrafish and goldfish. Irisin and RyR1b mRNA expression was downregulated by NLP in zebrafish cardiac and skeletal muscles. However, cardiac ATP2a2 mRNA expression was elevated after NLP injection. Administration of scrambled NLP did not affect irisin, RyR1b or ATP2a2 mRNA expression in zebrafish. Together, these results implicate NLP as a suppressor of cardiovascular physiology in zebrafish and goldfish.