Alterations in the hepatocyte epigenetic landscape in steatosis

Abstract

Fatty liver disease or the buildup of fat in the liver, has been reported to affect the global population. This comes with an increased risk for the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Yet, little is known about the effects of fat and alcohol diet towards epigenetic aging, with respect to changes in transcriptional and epigenomic profiles. In this study, we took up a multi-omics approach and integrated gene expression, methylation signals, and chromatin signals to study the epigenomic effects of a high-fat and alcohol-containing diet on mouse hepatocytes. We identified 4 relevant protein-protein interaction network clusters that were associated with relevant pathways that promote steatosis. Using a machine learning approach, we predict specific transcription factors that might be responsible to modulate the functionally relevant clusters. Finally, we discover 4 additional CpG loci and validate that aging related differential CpG methylation. Differential CpG methylation linked to aging showed minimal overlap with altered methylation in steatosis.