Vitamin E alleviates non-alcoholic fatty liver disease in phosphatidylethanolamine N-methyltransferase deficient mice

Publication date: Available online 6 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): 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 VeenAbstractPhosphatidylethanolamine 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 ceramid...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research