A high-fat diet alters genome-wide DNA methylation and gene expression in SM/J mice

BMC Genomics

James M. Cheverud¹  Lauren Hicks¹  Rabab Zaidi¹  Shyam Shah¹  Madeline Rose Keleher²  Xiaoyun Xing³  Daofeng Li³  Ting Wang³ 

[1] Department of Biology, Loyola University;Department of Evolution, Ecology, and Population Biology, Washington University in St. Louis;Department of Genetics, Washington University in St. Louis;

关键词: Obesity;    Mice;    Epigenetics;    Methylation;    RNA-seq;    Gene expression;   

DOI  :  10.1186/s12864-018-5327-0

来源: DOAJ

【 摘 要 】

Abstract Background While the genetics of obesity has been well defined, the epigenetics of obesity is poorly understood. Here, we used a genome-wide approach to identify genes with differences in both DNA methylation and expression associated with a high-fat diet in mice. Results We weaned genetically identical Small (SM/J) mice onto a high-fat or low-fat diet and measured their weights weekly, tested their glucose and insulin tolerance, assessed serum biomarkers, and weighed their organs at necropsy. We measured liver gene expression with RNA-seq (using 21 total libraries, each pooled with 2 mice of the same sex and diet) and DNA methylation with MRE-seq and MeDIP-seq (using 8 total libraries, each pooled with 4 mice of the same sex and diet). There were 4356 genes with expression differences associated with diet, with 184 genes exhibiting a sex-by-diet interaction. Dietary fat dysregulated several pathways, including those involved in cytokine-cytokine receptor interaction, chemokine signaling, and oxidative phosphorylation. Over 7000 genes had differentially methylated regions associated with diet, which occurred in regulatory regions more often than expected by chance. Only 5–10% of differentially methylated regions occurred in differentially expressed genes, however this was more often than expected by chance (p = 2.2 × 10− 8). Conclusions Discovering the gene expression and methylation changes associated with a high-fat diet can help to identify new targets for epigenetic therapies and inform about the physiological changes in obesity. Here, we identified numerous genes with altered expression and methylation that are promising candidates for further study.

【 授权许可】

Unknown