Title | Lipidomics and H2(18)O labeling techniques reveal increased remodeling of DHA-containing membrane phospholipids associated with abnormal locomotor responses in α-tocopherol deficient zebrafish (danio rerio) embryos. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | McDougall, MQ, Choi, J, Stevens, JF, Truong, L, Tanguay, RL, Traber, MG |
Journal | Redox Biol |
Volume | 8 |
Pagination | 165-74 |
Date Published | 2016 08 |
ISSN | 2213-2317 |
Keywords | alpha-Tocopherol, Animals, Behavior, Animal, Cell Membrane, Docosahexaenoic Acids, Embryo, Nonmammalian, Lipid Metabolism, Lysophospholipids, Metabolome, Metabolomics, Phenotype, Phospholipids, Vitamin E Deficiency, Zebrafish |
Abstract | We hypothesized that vitamin E (α-tocopherol) is required by the developing embryonic brain to prevent depletion of highly polyunsaturated fatty acids, especially docosahexaenoic acid (DHA, 22:6), the loss of which we predicted would underlie abnormal morphological and behavioral outcomes. Therefore, we fed adult 5D zebrafish (Danio rerio) defined diets without (E-) or with added α-tocopherol (E+, 500mg RRR-α-tocopheryl acetate/kg diet) for a minimum of 80 days, and then spawned them to obtain E- and E+ embryos. The E- compared with E+ embryos were 82% less responsive (p<0.01) to a light/dark stimulus at 96h post-fertilization (hpf), demonstrating impaired locomotor behavior, even in the absence of gross morphological defects. Evaluation of phospholipid (PL) and lysophospholipid (lyso-PL) composition using untargeted lipidomics in E- compared with E+ embryos at 24, 48, 72, and 120hpf showed that four PLs and three lyso-PLs containing docosahexaenoic acid (DHA), including lysophosphatidylcholine (LPC 22:6, required for transport of DHA into the brain, p<0.001), were at lower concentrations in E- at all time-points. Additionally, H2(18)O labeling experiments revealed enhanced turnover of LPC 22:6 (p<0.001) and three other DHA-containing PLs in the E- compared with the E+ embryos, suggesting that increased membrane remodeling is a result of PL depletion. Together, these data indicate that α-tocopherol deficiency in the zebrafish embryo causes the specific depletion and increased turnover of DHA-containing PL and lyso-PLs, which may compromise DHA delivery to the brain and thereby contribute to the functional impairments observed in E- embryos. |
DOI | 10.1016/j.redox.2016.01.004 |
Alternate Journal | Redox Biol |
PubMed ID | 26774753 |
PubMed Central ID | PMC4732018 |
Grant List | P30 ES000210 / ES / NIEHS NIH HHS / United States R01 HD062109 / HD / NICHD NIH HHS / United States S10 RR027878 / RR / NCRR NIH HHS / United States |