Institute for Cardiovascular Regeneration, Goethe-University, 60590, Frankfurt, Germany.
German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, 60590, Frankfurt, Germany.
Epigenetics Chromatin. 2023 Jul 6;16(1):30. doi: 10.1186/s13072-023-00504-8.
Fatty liver disease or the accumulation 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 a diet containing high fat and alcohol 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 four relevant gene 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 four additional CpG loci and validate aging-related differential CpG methylation. Differential CpG methylation linked to aging showed minimal overlap with altered methylation in steatosis.
脂肪肝疾病或肝脏脂肪堆积，据报道会影响全球人口。这会增加纤维化、肝硬化和肝细胞癌发展的风险。然而，对于高脂肪和酒精饮食如何影响表观遗传衰老，以及转录组和表观基因组谱的变化，人们知之甚少。在这项研究中，我们采用了多组学方法，整合了基因表达、甲基化信号和染色质信号，研究高脂肪和酒精饮食对小鼠肝细胞的表观基因组影响。我们确定了四个与促进脂肪变性的相关途径相关的相关基因网络簇。使用机器学习方法，我们预测可能负责调节功能相关簇的特定转录因子。最后，我们发现了四个额外的 CpG 位点，并验证了与衰老相关的差异 CpG 甲基化。与衰老相关的差异 CpG 甲基化与脂肪变性中的改变甲基化最小重叠。
