Postnatal Diet Remodels Hepatic DNA Methylation in Metabolic Pathways Established by a Maternal High-Fat Diet

Abstract

Aim: We investigate how postweaning diet may modify the epigenetic landscape to meet metabolic demands later in life. Methods: Sprague-Dawley rats were exposed to a high-fat (HF) diet during gestation and lactation. At weaning, male offspring were placed either on an HF diet (HF/HF) or a control diet (HF/C). Methylation-dependent immunoprecipitation sequencing and methylation-sensitive restriction enzyme sequencing were used to quantify hepatic DNA methylation. Results: Out of the 3966 identified differentially methylated regions, 37% were mapped to gene bodies while 6% fell within promoter or downstream regions. Differentially methylated genes were clustered in the type II diabetes mellitus and the adipocytokine signaling pathways. Conclusion: Our results indicate that compared with a lifelong HF diet, offspring exposed to a new postweaning control diet are able to remodel the hepatic epigenome, emphasizing the dynamic nature of the methylome even after early life.

Keywords::

• DNA methylation
• genome-wide
• MeDIP-seq
• metabolism
• MRE-seq

Acknowledgements

The authors thank T Wang at the Washington University, St. Louis, MO, for his technical support and guidance in the sequencing analysis.

Financial & competing interests disclosure

This project was supported by UIUC Research Board grant #12192 and the Data Purchase Program from the University Library. The authors wish to acknowledge the University Library at the University of Illinois at Urbana-Champaign, through the data purchasing grant, for providing support in generating the high-throughput dataset. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/epi-2017-0066

Additional information

Funding

This project was supported by UIUC Research Board grant #12192 and the Data Purchase Program from the University Library. The authors wish to acknowledge the University Library at the University of Illinois at Urbana-Champaign, through the data purchasing grant, for providing support in generating the high-throughput dataset. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.