High-fat diet caused widespread epigenomic differences on hepatic methylome in rat

Yukun Zhang, Huan Wang, Dan Zhou, Laura Moody, Stéphane Lezmi, Hong Chen, Yuan Xiang Pan

Research output: Contribution to journalArticlepeer-review


A high-fat (HF) diet is associated with progression of liver diseases. To illustrate genome-wide landscape of DNA methylation in liver of rats fed either a control or HF diet, two enrichment-based methods, namely methyl-DNA immunoprecipitation assay with high-throughput sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme sequencing (MRE-seq), were performed in our study. Rats fed with the HF diet exhibited an increased body weight and liver fat accumulation compared with that of the control group when they were 12 wk of age. Genome-wide analysis of differentially methylated regions (DMRs) showed that 12,494 DMRs induced by HF diet were hypomethylated and 6,404 were hypermethylated. DMRs with gene annotations [differentially methylated genes (DMGs)] were further analyzed to show gene-specific methylation profile. There were 88, 2,680, and 95 hypomethylated DMGs identified with changes in DNA methylation in the promoter, intragenic and downstream regions, respectively, compared with fewer hypermethylated DMGs (45, 1,623, and 50 in the respective regions). Some of these genes also contained an ACGT cis-acting motif whose DNA methylation status may affect gene expression. Pathway analysis showed that these DMGs were involved in critical hepatic signaling networks related to hepatic development. Therefore, HF diet had global impacts on DNA methylation profile in the liver of rats, leading to differential expression of genes in hepatic pathways that may involve in functional changes in liver development.

Original languageEnglish (US)
Pages (from-to)514-523
Number of pages10
JournalPhysiological genomics
Issue number10
StatePublished - Oct 1 2015


  • DMR
  • DNA hypomethylation
  • Gene expression
  • High-fat diet
  • MeDIP

ASJC Scopus subject areas

  • Physiology
  • Genetics


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