Epigenetic Network in Immunometabolic Disease

Although a large amount of data consistently shows that genes affect immunometabolic characteristics and outcomes, epigenetic mechanisms are also heavily implicated. Epigenetic changes, including DNA methylation, histone modification, and noncoding RNA, determine gene activity by altering the accessibility of chromatin to transcription factors. Various factors influence these alterations, including genetics, lifestyle, and environmental cues. Moreover, acquired epigenetic signals can be transmitted across generations, thus contributing to early disease traits in the offspring. A closer investigation is critical in this aspect as it can help to understand the underlying molecular mechanisms further and gain insights into potential therapeutic targets for preventing and treating diseases arising from immuno-metabolic dysregulation. In this review, the role of chromatin alterations in the transcriptional modulation of genes involved in insulin resistance, systemic inflammation, macrophage polarization, endothelial dysfunction, metabolic cardiomyopathy, and nonalcoholic fatty liver disease (NAFLD), is discussed. An overview of emerging chromatin-modifying drugs and the importance of the individual epigenetic profile for personalized therapeutic approaches in patients with immuno-metabolic disorders is also presented. Epigenetic mechanisms jointly influence immunometabolic characteristics. Epigenetic changes, encompassing DNA methylation, histone modification, and noncoding RNA, impact gene activity by modifying chromatin accessibility. These alterations are influenced by genetics, lifestyle, and environmental factors, with potential intergenerational effects. The review discusses chromatin alterations in genes related to various immunometabolic disorders and highlights emerging chromatin-modifying drugs, emphasizing personalized therapeutic approaches.image