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High Fat Diet Induced Genome‐wide Differential Methylation Affecting Hepatic Signaling Pathways In Rat
Author(s) -
Zhang Yukun,
Zhou Dan,
Ma Jian,
Pan YuanXiang,
Chen Hong
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.981.6
Subject(s) - methylated dna immunoprecipitation , dna methylation , differentially methylated regions , biology , methylation , epigenetics , gene , endocrinology , genetics , medicine , gene expression
High fat diet is associated with progression of liver diseases. We hypothesize that high fat diet changes genomic landscape of DNA methylation, leading to differential expression of genes in hepatic pathways involved in pathological development. Methyl‐DNA immunoprecipitation assay in combination with high‐throughput sequencing (MeDIP‐seq) and methylation‐sensitive restriction enzyme sequencing were applied to illustrate genomic landscape of DNA methylation that is modified by high fat diet in liver of control and high fat fed rats. Genome‐wide analysis of differentially methylated regions (DMR) showed that 8294 DMRs induced by high fat diet were hypomethylated and 4622 were hypermethylated. DMRs with gene annotations (DMG) were further analyzed to show gene‐specific methylation profile. There were 88, 2680, and 95 hypomethylated DMGs identified within promoter; intragenic and downstream regions, respectively, comparing to fewer hypermethylated DMGs (45, 1623, and 50 in the respective regions). Pathway analysis showed that DMGs were involved in inflammatory pathway, fibrosis development, insulin response, cell cycle control, and lipid metabolism. We for the first time analyzed the global impact of high fat diet on the DNA methylation profile in liver of rats. Our finding identified epigenetic mechanisms of the effects of high fat on critical signaling pathways related to liver functions.