TitleLethal dysregulation of energy metabolism during embryonic vitamin E deficiency.
Publication TypeJournal Article
Year of Publication2017
AuthorsMcDougall, M, Choi, J, Kim, H-K, Bobe, G, J Stevens, F, Cadenas, E, Tanguay, R, Traber, MG
JournalFree Radic Biol Med
Volume104
Pagination324-332
Date Published2017 03
ISSN1873-4596
KeywordsAnimals, Docosahexaenoic Acids, Energy Metabolism, Lipid Peroxidation, Mitochondria, Oxidation-Reduction, Vitamin E, Vitamin E Deficiency, Zebrafish
Abstract

Vitamin E (α-tocopherol, VitE) was discovered in 1922 for its role in preventing embryonic mortality. We investigated the underlying mechanisms causing lethality using targeted metabolomics analyses of zebrafish VitE-deficient embryos over five days of development, which coincided with their increased morbidity and mortality. VitE deficiency resulted in peroxidation of docosahexaenoic acid (DHA), depleting DHA-containing phospholipids, especially phosphatidylcholine, which also caused choline depletion. This increased lipid peroxidation also increased NADPH oxidation, which depleted glucose by shunting it to the pentose phosphate pathway. VitE deficiency was associated with mitochondrial dysfunction with concomitant impairment of energy homeostasis. The observed morbidity and mortality outcomes could be attenuated, but not fully reversed, by glucose injection into VitE-deficient embryos at developmental day one. Thus, embryonic VitE deficiency in vertebrates leads to a metabolic reprogramming that adversely affects methyl donor status and cellular energy homeostasis with lethal outcomes.

DOI10.1016/j.freeradbiomed.2017.01.020
Alternate JournalFree Radic. Biol. Med.
PubMed ID28095320
PubMed Central IDPMC5344700
Grant ListP30 ES000210 / ES / NIEHS NIH HHS / United States
S10 RR027878 / RR / NCRR NIH HHS / United States