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

Marcus Lyall, John Thomson, Jessy Cartier, Raffaele Ottaviano, Tim Kendall, Richard Meehan, Amanda Drake

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)61-71
Number of pages11
Issue number1-2
Publication statusPublished - 8 Aug 2019

Keywords / Materials (for Non-textual outputs)

  • 5-Methylcytosine/analogs & derivatives
  • Animals
  • DNA Methylation
  • Diet, High-Fat/adverse effects
  • Liver/metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease/etiology
  • Phenotype
  • Transcriptome


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