Lactylation: novel epigenetic regulatory and therapeutic opportunities

Lactate, which is an end product of glycolysis, has traditionally been considered a metabolic waste. However, numerous studies have demonstrated that lactate serves metabolic and nonmetabolic functions in physiological processes and multiple diseases. Cancer and pulmonary arterial hypertension have been shown to undergo metabolic reprogramming, which is accompanied by increased lactate production. Metabolic reprogramming and epigenetic modifications have been extensively linked; furthermore, posttranslational modifications of histones caused by metabolites play a vital role in epigenetic alterations. In this paper, we reviewed recent research on lactate-induced histone modifications and provided a new vision about the metabolic effect of glycolysis. Based on our review, the cross talk between the metabolome and epigenome induced by glycolysis may indicate novel epigenetic regulatory and therapeutic opportunities. There is a magnificent progress in the interaction between metabolomics and epigenomics in recent decades, but many questions still remained to be investigated. Lactylation is found in different pathophysiological states and leads to diverse biological effects; however, only a few mechanisms of lactylation have been illustrated. Further research on lactylation would provide us with a better understanding of the cross talk between metabolomics and epigenomics.