Document Type
Article
Publication Date
12-7-2018
Publication Title
BMC Genomics
Pages
1-13
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.
Identifier
ISSN: 1471-2164
Recommended Citation
Keleher, Madeline R.; Zaidi, Rabab; Hicks, Lauren; Shah, Shyam; Xing, Xiaoyun; Li, Daofeng; Wang, Ting; and Cheverud, James M.. A High-Fat Diet Alters Genome-Wide DNA Methylation and Gene Expression in SM/J Mice. BMC Genomics, , : 1-13, 2018. Retrieved from Loyola eCommons, Biology: Faculty Publications and Other Works, http://dx.doi.org/10.1186/s12864-018-5327-0
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright Statement
© The Authors, 2018.
Comments
Author Posting © The Authors, 2018. This article is posted here by permission of BioMed Central for personal use, not for redistribution. The article was published in BMC Genomics, Volume 19, December 2018, https://doi.org/10.1186/s12864-018-5327-0