title: High-fat diet caused widespread epigenomic differences on hepatic methylome in rat.
abstract: 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.
authors.affiliation: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, Illinois;
authors.forename: Yukun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, Illinois;
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, Illinois;
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois;
authors.forename: Laura
authors.initials: L
authors.lastname: Moody
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lezmi
authors.affiliation: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, Illinois; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois;
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, Illinois; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois; Illinois Informatics Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois; and yxpan@illinois.edu.
authors.forename: Yuan-Xiang
authors.initials: YX
authors.lastname: Pan
mesh_terms: D050154:Adiposity / Q000235:genetics; D000818:Animals; D001835:Body Weight / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D059305:Diet, High-Fat; D044127:Epigenesis, Genetic; D005260:Female; D008099:Liver / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: C470699:Chrna10 protein, rat; D011978:Receptors, Nicotinic
keywords: DMR; DNA hypomethylation; MeDIP; gene expression; high-fat diet