Epigenetic regulation by ketone bodies in cardiac diseases and repair

Ketone bodies, particularly β-hydroxybutyrate (BHB), play an important role in the epigenetic regulation of gene expression in cardiac tissues, impacting both cardiac health and disease. This review explores the multifaceted influence of ketone bodies on epigenetic mechanisms, including histone acetylation, DNA methylation, ubiquitination, sirtuins activation, and RNA modulation. By acting as endogenous histone deacetylase inhibitors, ketone bodies enhance histone acetylation, thereby promoting the expression of genes involved in antioxidant defenses, anti-inflammatory responses, and metabolic regulation. Furthermore, BHB affects DNA methylation patterns by altering the availability of key metabolites such as S-adenosylmethionine. Ketogenic diet, which elevates BHB levels, has been shown to modulate gene expression, such as increasing FOXO3a and metallothionein 2, and improve cardiac function. This review highlights the therapeutic potential of ketone bodies in managing cardiac diseases through their epigenetic effects, underscoring the need for further research to elucidate the detailed molecular pathways and long-term impacts of these metabolic interventions.