Resveratrol alleviates non-alcoholic fatty liver disease through epigenetic modification of the Nrf2 signaling pathway.
Animals
Antioxidants
/ pharmacology
Decitabine
/ pharmacology
Diet, High-Fat
Disease Models, Animal
Epigenesis, Genetic
Hep G2 Cells
Humans
Kelch-Like ECH-Associated Protein 1
/ metabolism
Lipogenesis
/ drug effects
Male
Mice
Mice, Inbred C57BL
NF-E2-Related Factor 2
/ biosynthesis
Non-alcoholic Fatty Liver Disease
/ drug therapy
Random Allocation
Resveratrol
/ pharmacology
Signal Transduction
/ drug effects
HFD fed mice
HepG2
Keap1
Methylation
Non-alcoholic fatty liver disease
Nrf2
Resveratrol
Journal
The international journal of biochemistry & cell biology
ISSN: 1878-5875
Titre abrégé: Int J Biochem Cell Biol
Pays: Netherlands
ID NLM: 9508482
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
14
09
2019
revised:
02
12
2019
accepted:
11
12
2019
pubmed:
16
12
2019
medline:
27
3
2020
entrez:
16
12
2019
Statut:
ppublish
Résumé
Recent findings have demonstrated the aberrant DNA methylation of the Nrf2-Keap1 genes in human cancers; however, the epigenetic control of this pathway in non-alcoholic fatty liver disease (NAFLD) is unknown. Resveratrol can modify epigenetic mechanisms. Our objectives in this study were to explore the correlation between promoter methylation of the Nrf2-Keap1 genes and NAFLD, and that investigate the effect of resveratrol on the epigenetic regulation Nrf2-Keap1 in vitro and in vivo models of NAFLD. Resveratrol attenuated high fat-diet (HFD)-induced methylation of the Nrf2 promoter in the liver of mice, and this effect was correlated with reduction in triglyceride level and decrease in the expression of lipogenesis-related genes such as FAS and SREBP-1c. In addition, treatment of HepG2 cells with high glucose (HG) enhanced methylation level of the Nrf2 promoter, whereas resveratrol reversed this effect. Treatment of the cells with resveratrol or 5-aza, a demethylating agent, could prevent HG-induced reactive oxygen species production and expression of Nrf2-controlled antioxidant genes. Moreover, resveratrol or 5-aza could significantly attenuate HG-induced triglyceride accumulation in HepG2 cells. These findings indicate that resveratrol attenuates NAFLD through the epigenetic modification the Nrf2 signaling.
Identifiants
pubmed: 31838177
pii: S1357-2725(19)30244-4
doi: 10.1016/j.biocel.2019.105667
pii:
doi:
Substances chimiques
Antioxidants
0
Keap1 protein, mouse
0
Kelch-Like ECH-Associated Protein 1
0
NF-E2-Related Factor 2
0
Nfe2l2 protein, mouse
0
Decitabine
776B62CQ27
Resveratrol
Q369O8926L
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105667Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.