Metabolic Memory in Oral Inflammation

Absztrakt

The global rise in metabolic diseases has increased the severity and therapeutic complexity of oral inflammatory disorders. Persistent inflammation driven by metabolic memory presents a central pathological mechanism. Even after metabolic parameters are normalized, abnormal gene expression can persist, leading to prolonged disease progression and recurrent episodes. In the oral cavity, metabolic memory is most clearly evident in periodontitis and impaired wound healing, where sustained immune dysregulation and tissue destruction remain after hyperglycemia or hyperlipidemia has been corrected. Epigenetic reprogramming presents a key molecular mechanism of metabolic memory, including DNA methylation, histone modifications, and expression of noncoding RNAs. The epigenetic alterations collectively reprogram immune cell function, driving the dysregulation of innate and adaptive immunity while influencing the fate of oral stromal cells and epithelial cells. Prolonged inflammation contributes to an altered host–microbiota interaction, reinforcing disease persistence and treatment resistance. Metabolic disorders induce coordinated epigenetic changes that can be grouped into permissive and repressive events affecting gene transcription. Permissive events include increased histone acetylation, enrichment of activating histone methylation marks (e.g., H3K4me3), and DNA demethylation at inflammatory gene loci. These modifications promote an open chromatin structure to enhance transcription factor access. Repressive events include increased DNA methylation and enrichment of repressive histone methylation marks (e.g., H3K9me3). DNA methylation typically occurs in promoter regions of genes, and repressive histone changes lead to the formation of compact chromatin, both of which reduce transcriptional activity. Noncoding RNAs generally decrease target messenger RNA stability or inhibit translation further, reinforcing a repressive effect. The combined effect of these modifications is a shift in protein expression that reinforces chronic inflammatory signaling in abnormal metabolic conditions. This review comprehensively summarizes the epigenetic mechanisms by which metabolic memory sustains oral inflammation at molecular, cellular, and tissue levels, as well as potential preventive and therapeutic interventions.