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Vitamin E does not prevent Western diet-induced NASH progression and increases metabolic flux dysregulation in mice
Vitamin E does not prevent Western diet-induced NASH progression and increases metabolic flux dysregulation in mice
Clinton M. Hasenour
(Departments of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN)
Arion J. Kennedy
(Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN)
Tomasz Bednarski
(Departments of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN)
Irina A. Trenary
(Departments of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN)
Brandon J. Eudy
(Department of Food Science and Human Nutrition, University of Florida, Gainesville, FL)
Robin P. da Silva
(Department of Food Science and Human Nutrition, University of Florida, Gainesville, FL)
Kelli L. Boyd
(Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN)
Jamey D. Young
(To whom correspondence should be addressed; Departments of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN; Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN; Mouse Metabolic Phenotyping Center, Vanderbilt University, Nashville, TN; To whom correspondence should be addressed)
Journal: Journal of Lipid Research
•
• Elsevier
• ISSN: 0022-2275
Abstract
Fatty liver involves ectopic lipid accumulation and dysregulated hepatic oxidative metabolism, which can progress to a state of elevated inflammation and fibrosis referred to as nonalcoholic steatohepatitis (NASH). The factors that control progression from simple steatosis to NASH are not fully known. Here, we tested the hypothesis that dietary vitamin E (VitE) supplementation would prevent NASH progression and associated metabolic alterations induced by a Western diet (WD). Hyperphagic melanocortin-4 receptor-deficient (MC4R−/−) mice were fed chow, chow+VitE, WD, or WD+VitE starting at 8 or 20 weeks of age. All groups exhibited extensive hepatic steatosis by the end of the study (28 weeks of age). WD feeding exacerbated liver disease severity without inducing proportional changes in liver triglycerides. Eight weeks of WD accelerated liver pyruvate cycling, and 20 weeks of WD extensively upregulated liver glucose and oxidative metabolism assessed by 2H/13C flux analysis. VitE supplementation failed to reduce the histological features of NASH. Rather, WD+VitE increased the abundance and saturation of liver ceramides and accelerated metabolic flux dysregulation compared with 8 weeks of WD alone. In summary, VitE did not limit NASH pathogenesis in genetically obese mice, but instead increased some indicators of metabolic dysfunction.
Clinton M. Hasenour, Arion J. Kennedy, Tomasz Bednarski, et al. (2020). "Vitamin E does not prevent Western diet-induced NASH progression and increases metabolic flux dysregulation in mice". Journal of Lipid Research. https://doi.org/10.1194/jlr.ra119000183