Choi J, Leonard SW, Kasper K, McDougall M, Stevens JF, Tanguay RL, Traber MG (2015) J Lipid Res. doi: 10.1194/jlr.M058941
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 added vitamin E (E+, 500 mg RRR-α-tocopheryl acetate/kg 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) compared with E+ brains (6.5 ± 0.9 mg/g, mean ± SEM, n=10/group, P=0.04). Using lipidomics, 155 lipids in brain extracts were identified. Only four PL 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 lysoPL (combined P=0.0003), which are critical for membrane PL remodeling. Thus, E- brains contained less DHA-PL, more hydroxy-DHA-PC and fewer lyso-PLs, suggesting that lipid peroxidation depletes membrane DHA-PC and homeostatic mechanisms to repair the damage result in lyso-PL depletion.