Positive Health Online

Abstract

MCDOUGALL and COLLEAGUES, 1. Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 97331, USA; 2. Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; 3. The Catholic University of Korea, Seoul, Republic of Korea; 4. Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA; Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, USA; 5. University of Southern California, School of Pharmacy, Los Angeles, CA 90089, USA; 6. Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, USA; Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA; Sinnhuber Aquatic Research Laboratory, Oregon State University, Corvallis, OR 97331, USA; 7. Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 97331, USA; Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, USA. maret.traber@oregonstate.edu studied lethal dysregulation of energy metabolism during Vitamin E (α-tocopherol, VitE) deficiency.

Background

Vitamin E (α-tocopherol, VitE) was discovered in 1922 for its role in preventing embryonic mortality.

Methodology

We investigated the underlying mechanisms causing death using targeted metabolomics analyses of zebrafish VitE-deficient embryos over five days of development, which coincided with their increased morbidity and mortality.

Results

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.

Conclusion

Thus, embryonic VitE deficiency in vertebrates leads to a metabolic reprogramming that adversely affects methyl donor status and cellular energy homeostasis with lethal outcomes.

References

McDougall M1, Choi J2, Kim HK3, Bobe G2, Stevens JF4, Cadenas E5, Tanguay R6, Traber MG7. Lethal dysregulation of energy metabolism during embryonic vitamin E deficiency. Free Radic Biol Med.104:324-332. Mar 2017. DOI: 10.1016/j.freeradbiomed.2017.01.020. Epub Jan 14 2017. https://www.ncbi.nlm.nih.gov/pubmed/28095320