期刊
EPIGENETICS
卷 15, 期 1-2, 页码 61-71出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15592294.2019.1649527
关键词
Obesity; NAFLD; methylation; hydroxymethylation; steatosis
资金
- Wellcome Trust PhD Fellowship as part of the Edinburgh Clinical Academic Track scheme [102839/Z/13/Z]
- Wellcome Trust Intermediate Fellowship [095898/Z/11/Z]
- Medical Research Council [MC_PC_U127574433]
- CEFIC grant
- Scottish Senior Clinical Fellowship [SCD/09]
- British Heart Foundation Centre for Research Excellence
- Innovative Medicine Initiative Joint Undertaking (IMI JU) [115001]
- Wellcome Trust [102839/Z/13/Z] Funding Source: Wellcome Trust
- MRC [MC_UU_00007/17, MC_PC_U127574433] Funding Source: UKRI
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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