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

Redox Biology
Melissa McDougallMaret G Traber

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-con...Continue Reading

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Citations

Feb 10, 2017·Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme·Vincent P GeorgescuSteven R McAnulty
Jan 18, 2017·Free Radical Biology & Medicine·Melissa McDougallMaret G Traber
May 29, 2018·Genes & Development·Marcus ConradBrent R Stockwell
Sep 23, 2020·Scientific Reports·Brian HeadMaret G Traber
Aug 22, 2020·American Journal of Respiratory Cell and Molecular Biology·Shotaro MatsumotoJeffrey E Gotts
Sep 22, 2020·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·David A DreierChristopher J Martyniuk
Jun 14, 2021·The Journal of Nutritional Biochemistry·Alexander T WattMaret G Traber
Jun 12, 2021·Annual Review of Nutrition·William S BlanerMaret G Traber
Apr 21, 2020·Ecotoxicology and Environmental Safety·Filomena MottolaLucia Rocco

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Software Mentioned

R Developmental Core
Viewpoint Zebrabox
ZAAP
Metaboanalyst
GraphPad Prism
PeakView
R scripts
R Developmental Core Team
R

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