Lethal dysregulation of energy metabolism during embryonic vitamin E deficiency

Free Radic Biol Med. 2017 Mar;104:324-332. doi: 10.1016/j.freeradbiomed.2017.01.020. Epub 2017 Jan 14.


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.

Keywords: Docosahexaenoic acid; Methyl donors; Mitochondria; Oxygen consumption; Phosphatidylcholine; α-tocopherol.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Docosahexaenoic Acids / metabolism
  • Energy Metabolism*
  • Lipid Peroxidation / genetics
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Oxidation-Reduction
  • Vitamin E / genetics
  • Vitamin E / metabolism*
  • Vitamin E Deficiency / embryology
  • Vitamin E Deficiency / genetics*
  • Vitamin E Deficiency / metabolism
  • Vitamin E Deficiency / pathology
  • Zebrafish / embryology
  • Zebrafish / genetics*


  • Vitamin E
  • Docosahexaenoic Acids