ZFIN ID: ZDB-PUB-160118-3
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
McDougall, M.Q., Choi, J., Stevens, J.F., Truong, L., Tanguay, R.L., Traber, M.G.
Date: 2016
Source: Redox Biology 8: 165-174 (Journal)
Registered Authors: Tanguay, Robert L.
Keywords: Brain, Development, Docosahexaenoic acid, H(2)(18)O, Mass spectrometry, Peroxidation, Phospholipids, Vitamin E
MeSH Terms:
  • Animals
  • Behavior, Animal
  • Cell Membrane/metabolism
  • Docosahexaenoic Acids/metabolism*
  • Embryo, Nonmammalian
  • Lipid Metabolism*
  • Lysophospholipids/metabolism
  • Metabolome
  • Metabolomics*/methods
  • Phenotype
  • Phospholipids/metabolism*
  • Vitamin E Deficiency/metabolism*
  • Zebrafish/metabolism*
  • alpha-Tocopherol/metabolism*
PubMed: 26774753 Full text @ Redox Biol.
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.