Rat liver epigenome programing by perinatal exposure to 2,2',4'4'-tetrabromodiphenyl ether.

Perinatal exposures to polybrominated diphenyl ethers permanently reprogram liver metabolism and induce a nonalcoholic fatty liver disease-like phenotype and insulin resistance in rodents. To test if these changes are associated with altered liver epigenome. 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. 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. Changes in the liver epigenome are a likely candidate mechanism of long-term maintenance of an aberrant metabolic phenotype.