Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

Several studies have described phenotypic changes in the offspring of mice exposed to a variety of environmental factors, including diet, toxins, and stress; however, the molecular pathways involved in these changes remain unclear. Using a high fat diet (HFD)-induced obesity mouse model, we examined liver gene expression in male offspring and analyzed chromatin of paternal spermatozoa. We found that the hepatic mRNA level of 7 genes (out of 20 evaluated) was significantly altered in HFD male offspring compared to control mice, suggesting that phenotypic changes in the offspring depend on parental diet. We examined seven imprinted loci in spermatozoa DNA from HFD-treated and control fathers by bisulfite sequencing, but did not detect changes in DNA methylation associated with HFD. Using chromatin immunoprecipitation followed by high-throughput sequencing, we found differential histone H3-occupancy at genes involved in the regulation of embryogenesis and differential H3K4me1-enrichment at transcription regulatory genes in HFD fathers versus control mice. These results suggest that dietary exposure can modulate histone composition at regulatory genes implicated in developmental processes.