Rat Liver Epigenome Programing by Perinatal Exposure to 2,2′,4′4′-Tetrabromodiphenyl Ether

Abstract

Perinatal exposures to polybrominated diphenyl ethers permanently reprogram liver metabolism and induce a nonalcoholic fatty liver disease-like phenotype and insulin resistance in rodents. Aim: To test if these changes are associated with altered liver epigenome. Materials & methods: Expression of small RNA and changes in DNA methylation in livers of adult rats were analyzed following perinatal exposure to 2,2′,4,4′-tetrabromodiphenyl ether, the polybrominated diphenyl ether congener most prevalent in human tissues. Results: We identified 33 differentially methylated DNA regions and 15 differentially expressed miRNAs. These changes were enriched for terms related to lipid and carbohydrate metabolism, insulin signaling, Type-2 diabetes and nonalcoholic fatty liver disease. Conclusion: Changes in the liver epigenome are a likely candidate mechanism of long-term maintenance of an aberrant metabolic phenotype.

Keywords::

• 2,2′,4,4′-tetrabromodiphenyl ether
• BDE-47
• developmental programing
• DNA methylation
• liver metabolism
• NAFLD
• nonalcoholic fatty liver
• PBDE
• polybrominated diphenyl ethers
• small RNA

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2019-0315

Acknowledgments

The authors are very thankful to Joseph McGaunn for proofreading of the manuscript and useful comments.

Financial & competing interests disclosure

This study was supported by the Russian Science Foundation (grant nos. #14-45-00065 for DNA methylation and 18-15-00202 for small RNA). All the authors declare that they do not have any relationships (personal, academic or financial relationships that could influence their actions) or financial involvement with an organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Ethical conduct of research

All procedures met the guidelines of the National Institutes of Health Guide for the Care and Use of Laboratory Animals and this study was approved by the Institutional Animal Care and Use Committee at University of Massachusetts, Amherst.

Additional information

Funding

This study was supported by the Russian Science Foundation (grant nos. #14-45-00065 for DNA methylation and 18-15-00202 for small RNA). All the authors declare that they do not have any relationships (personal, academic or financial relationships that could influence their actions) or financial involvement with an organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.