Lactylation and lactate: insights into muscle cell epigenetic regulators in exercise

Lactate was once regarded as a metabolic waste. However, recent studies have established its dual role as both a versatile signaling molecule and a substrate for a novel post-translational modification (PTMs)-lysine lactylation. Exercise, as a primary physiological stimulus for lactate production, provides an ideal context for exploring lactate-mediated epigenetic regulation. This regulatory mechanism is particularly relevant in muscle cells, which serve as both the main producers and consumers of lactate. This review focuses on three core muscle cell types: skeletal muscle cells, cardiomyocytes and vascular smooth muscle cells (VSMCs). We systematically elucidate the functional roles of the lactate-lactylation in these cells, examining how lactate can regulate cellular adaptation and pathological processes both independently and in concert with other PTMs. Furthermore, we analyze the distinct effects of diferent exercise modalities (ranging from moderate training to overtraining) on the lactylation dynamics, revealing its the dual functions of lactylation in exercise physiology and pathology. By integrating these mechanisms, this review provides a novel theoretical framework for understanding exercise-mediated muscle cell function and offers fresh perspectives for intervention strategies targeting metabolic and cardiovascular diseases.