Non-alcoholic fatty liver disease (NAFLD) is associated with dynamic changes in DNA hydroxymethylation.

Epigenetics : Official Journal of the DNA Methylation Society
Marcus J LyallAmanda J Drake

Abstract

Non-alcoholic fatty liver disease (NAFLD) is now the commonest cause of liver disease in developed countries affecting 25-33% of the general population and up to 75% of those with obesity. Recent data suggest that alterations in DNA methylation may be related to NAFLD pathogenesis and progression and we have previously shown that dynamic changes in the cell lineage identifier 5-hydroxymethylcytosine (5hmC) may be important in the pathogenesis of liver disease. We used a model of diet-induced obesity, maintaining male mice on a high-fat diet (HFD) to generate hepatic steatosis. We profiled hepatic gene expression, global and locus-specific 5hmC and additionally investigated the effects of weight loss on the phenotype. HFD led to increased weight gain, fasting hyperglycaemia, glucose intolerance, insulin resistance and hepatic periportal macrovesicular steatosis. Diet-induced hepatic steatosis associated with reversible 5hmC changes at a discrete number of functionally important genes. We propose that 5hmC profiles are a useful signature of gene transcription and a marker of cell state in NAFLD and suggest that 5hmC profiles hold potential as a biomarker of abnormal liver physiology.

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Citations

Sep 8, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Mohsen AfaridehLilach O Lerman
May 10, 2020·Scientific Reports·Jesús Rafael Rodríguez-AguileraHéctor Hernández-Vargas
Nov 5, 2020·International Journal of Molecular Sciences·Jeongeun Hyun, Youngmi Jung
Dec 23, 2020·European Journal of Clinical Investigation·Xiaofang ZhangMohsen Ghanbari
Feb 12, 2021·International Journal of Environmental Research and Public Health·Małgorzata MoszakPaweł Bogdański
Apr 4, 2021·International Journal of Molecular Sciences·Ioannis I MoustakasAntonios Chatzigeorgiou
May 1, 2021·International Journal of Molecular Sciences·Maria NotarnicolaCaterina Messa

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Methods Mentioned

BETA
biopsy
immunoprecipitation
hMeDIP-seq
biopsies
ELISA
PCR
Chip

Software Mentioned

Heatmap
Prism
ARRIVE
ggplot2
Base R
Limma Package
Ion Torrent suite
R
gplots
GraphPad

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