Effects of programming on the hepatic epigenome by maternal low‐fat diet persist in adult offspring fed an obesogenic diet

Obesity and metabolic disease present a risk to long‐term health outcomes. Epigenetic marks such as DNA methylation are established during early life and have effects on later life through developmental programming. In the present study, we examined whether maternal diet alters DNA methylation and whether such modifications persist after an obesogenic postnatal dietary challenge. During gestation and lactation, male Sprague Dawley rats were exposed to either a high‐fat diet (HF; n = 10) or low‐fat diet (LF; n = 10). After weaning, all animals were fed the HF diet until postnatal week 12. There were no differences observed in food intake or body weight between the two groups of offspring animals. Hepatic DNA methylation was quantified using both Methylated DNA Immunoprecipitation sequencing (MeDIP‐seq) and Methylation‐sensitive Restriction Enzyme sequencing (MRE‐seq). Overall, 1,419 differentially methylated regions (DMRs) were identified. DMRs tended to be located in CpG shores, as opposed to CpG islands, and were enriched for genes involved in metabolism and cancer. Gene expression was measured for 31 candidate genes in these pathways. Among these, Map3k5 and Igf1r were confirmed to be differentially expressed. When the functional relevance of intergenic DMRs was quantified using chromatin contact data, we discovered that conserved DMRs were topologically associated with metabolism genes, which was associated with differential expression of Adh5, Enox1, and Pik3c3. Overall, although maternal dietary fat was unable to reverse offspring weight gain in response to postnatal obesogenic diet, early life diet did program the hepatic methylome. Epigenetic alterations on the hepatic methylome occur primarily in metabolic and cancer pathways and are associated with altered gene expression. Physiological consequences of these epigenetic marks will require future investigations for a better understanding of epigenomic programming. Support or Funding Information This project was supported by UIUC Research Board grant #12192, the USDA Cooperative State Research, Education and Extension Service, Hatch project numbers # ILLU‐698‐923 and ILLU‐698‐369, ILLU‐698‐391, and the Data Purchase Program from the University of Illinois Library. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .