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Publication
Vitamin E does not prevent Western diet-induced NASH progression and increases
metabolic flux dysregulation in mice.
Authors Hasenour CM, Kennedy AJ, Bednarski T, Trenary IA, Eudy BJ, DaSilva RP, Boyd KL,
Young JD
Submitted By Submitted Externally on 3/26/2020
Status Published
Journal Journal of lipid research
Year 2020
Date Published 2/1/2020
Volume : Pages Not Specified : Not Specified
PubMed Reference 32086244
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 wks of age. All
groups exhibited extensive hepatic steatosis by the end of the study (28 wks 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 wks 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 wks of WD alone. In summary, VitE did not limit
NASH pathogenesis in genetically obese mice, but instead increased some
indicators of metabolic dysfunction.





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