Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain lysophospholipids discovered using lipidomics

We hypothesized that brains from vitamin E-deficient (E-) zebrafish (Danio rerio) would undergo increased lipid peroxidation because they contain highly polyunsaturated fatty acids, thus susceptible lipids could be identified. Brains from zebrafish fed for 9 months defined diets without (E-) or with (E+) added vitamin E (500 mg RRR-alpha-tocopheryl acetate per kilogram diet) were studied. Using an untargeted approach, 1-hexadecanoyl-2-docosahexaenoyl-sn -glycero-3-phosphocholine [DHA-PC 38: 6, PC 16:0/22:6] was the lipid that showed the most significant and greatest fold-differences between groups. DHA-PC concentrations were approximately 1/3 lower in E- (4.3 +/- 0.6 mg/g) compared with E+ brains (6.5 +/- 0.9 mg/g, mean +/- SEM, n = 10 per group, P = 0.04). Using lipidomics, 155 lipids in brain extracts were identified. Only four phospholipids (PLs) were different (P < 0.05) between groups; they were lower in E-brains and contained DHA with DHA-PC 38: 6 at the highest abundances. Moreover, hydroxy-DHA-PC 38: 6 was increased in E-brains (P = 0.0341) supporting the hypothesis of DHA peroxidation. More striking was the depletion in E-brains of nearly 60% of 19 different lysophospholipids (lysoPLs) (combined P = 0.0003), which are critical for membrane PL remodeling. Thus, E-brains contained fewer DHA-PLs, more hydroxy-DHA-PCs, and fewer lysoPLs, suggesting that lipid peroxidation depletes membrane DHA-PC and homeostatic mechanisms to repair the damage resulting in lysoPL depletion