L-6 Vitamin E deficiency causes a metabolic reprogramming dysregulating cellular energy homeostasis

Publication date: July 2017
Source:Free Radical Biology and Medicine, Volume 108, Supplement 1
Author(s): Maret G. Traber, Melissa McDougall, Jaewoo Choi, Hye-Kyeong Kim, Gerd Bobe, J. Frederik Stevens, Enrique Cadenas, Robert Tanguay
Vitamin E (α-tocopherol, VitE) was discovered in 1922 because it prevented rat fetal resorption. We investigated the mechanisms causing lethality using targeted metabolomic analyses of zebrafish VitE-deficient embryos daily from 1 to 5 days by which time 80% experienced increased morbidity or mortality. VitE deficiency caused lipid peroxidation of docosahexaenoic acid (DHA), depleted DHA-containing phospholipids, especially phosphatidylcholine, and depleted choline. It also increased NADPH oxidation, leading to glucose depletion by shunting it to the pentose phosphate pathway. VitE deficiency caused impairment of oxygen consumption and energy homeostasis. The observed morbidity outcomes could be attenuated 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.



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