Vitamin E alleviates non-alcoholic fatty liver disease in phosphatidylethanolamine N-methyltransferase deficient mice |
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Authors: | Natalia Presa Robin D Clugston Susanne Lingrell Samuel E Kelly Alfred H Merrill Sayantan Jana Zamaneh Kassiri Antonio Gómez-Muñoz Dennis E Vance Rene L Jacobs Jelske N van der Veen |
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Institution: | 1. Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country, P.O. Box 644, 48980 Bilbao, Spain;2. Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, AB, Canada;3. Department of Physiology, University of Alberta, Edmonton, AB, Canada;4. Department of Biochemistry, University of Alberta, Edmonton, AB, Canada;5. Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, AB, Canada;6. School of Biological Sciences and the Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30338, USA |
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Abstract: | Phosphatidylethanolamine N-methyltransferase (PEMT) converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC), mainly in the liver. Pemt?/? mice are protected from high-fat diet (HFD)-induced obesity and insulin resistance, but develop severe non-alcoholic fatty liver disease (NAFLD) when fed a HFD, mostly due to impaired VLDL secretion. Oxidative stress is thought to be an essential factor in the progression from simple steatosis to steatohepatitis. Vitamin E is an antioxidant that has been clinically used to improve NAFLD pathology. Our aim was to determine whether supplementation of the diet with vitamin E could attenuate HFD-induced hepatic steatosis and its progression to NASH in Pemt?/? mice. Treatment with vitamin E (0.5?g/kg) for 3?weeks improved VLDL-TG secretion and normalized cholesterol metabolism, but failed to reduce hepatic TG content. Moreover, vitamin E treatment was able to reduce hepatic oxidative stress, inflammation and fibrosis. We also observed abnormal ceramide metabolism in Pemt?/? mice fed a HFD, with elevation of ceramides and other sphingolipids and higher expression of mRNAs for acid ceramidase (Asah1) and ceramide kinase (Cerk). Interestingly, vitamin E supplementation restored Asah1 and Cerk mRNA and sphingolipid levels. Together this study shows that vitamin E treatment efficiently prevented the progression from simple steatosis to steatohepatitis in mice lacking PEMT. |
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Keywords: | Non-alcoholic fatty liver disease Oxidative stress Vitamin E Antioxidant Phosphatidylcholine Ceramide |
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