Abstract: In this study, in order to investigate the phospholipid composition characteristics and hypoglycemic activity of krill oil, we determined the content of total phospholipids in krill oil by a colorimetric method, examined the phospholipid composition by high-resolution mass spectrometry, and then applied the mass spectral fragmentation pattern and the databases Lipidmaps and Lipidblast for structural analysis. Furthermore, we evaluated the effect of krill oil on blood glucose, biochemical indexes and gene expression levels related to the regulation of blood glucose in a zebrafish model of hyperglycemia induced by the combined treatment of alloxan and sucrose, and explored the potential sites of hypoglycemic action of krill oil-specific phospholipid docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) by molecular docking. The results showed that the content of phospholipids in cold-extracted krill oil was 57.57%, and a total of 63 phospholipids were identified, of which phosphatidylcholine (PC) was the most abundant. Krill oil significantly reduced blood glucose concentration, elevated insulin and glycogen levels, inhibited the expression of FOXO1/PCK1/G6PC, and promoted the expression of GLUT4 in hyperglycemic zebrafish. Molecular docking revealed that DHA and EPA in krill oil might act at the FOXO1/PCK1/G6PC sites, suggesting close relationship between the phospholipid components and the hypoglycemic activity of krill oil. In summary, this study found that cold-extracted krill oil is rich in phospholipids and is a potential natural product with good hypoglycemic effect.

Key words: krill oil; phospholipid; high-resolution mass spectrometry; hypoglycemic; zebrafish model