Abstract
Epigenetic modifications, including deoxyribonucleic acid (DNA) methylation, histone modifications, and non-coding ribonucleic acid (ncRNAs), regulate gene expression without altering the DNA sequence and play pivotal roles in the pathogenesis of metabolic disorders (MDs), such as diabetes, obesity, and cardiovascular diseases. This review aims to consolidate the current knowledge on the epigenetic mechanisms underlying MDs, emphasizing histone modifications and ncRNAs. A comprehensive literature search was conducted using the PubMed, Scopus, and Web of Science databases. Studies published between 2000 and 2024 (a few foundational and historical articles were also added) were screened using search terms such as "epigenetics AND metabolic disorders," "DNA methylation AND diabetes," "histone modifications AND obesity," and "non-coding RNA AND cardiovascular diseases." Relevant translational and clinical studies were reviewed to synthesize the existing evidence on the epigenetic regulation of metabolic diseases. Histone modifications, including acetylation, methylation, phosphorylation, and ubiquitination, contribute to metabolic dysregulation by modulating chromatin accessibility and gene transcription. Additionally, ncRNAs, such as microRNAs, long ncRNAs, and circular RNAs, influence metabolic pathways by post-transcriptionally regulating key genes involved in insulin resistance, lipid metabolism, and inflammation. Emerging research highlights the potential of epigenetic biomarkers for early disease detection and prognosis, as well as the therapeutic potential of epigenetic modulators, including histone deacetylase inhibitors and DNA methylation-targeting agents. Despite promising advances, challenges remain in translating epigenetic findings into clinical practice because of inter-individual variability and the complex interplay between genetics and environmental factors. Future research should focus on large-scale, multicenter studies to validate epigenetic biomarkers and develop personalized epigenetic interventions for MDs.