New insights into lactate in exercise adaptations: does protein lactylation play a role?

Physical activity and exercise are widely recognized as effective ways to promote physical fitness and prevent disease; however, their underlying molecular mechanisms remain to be fully elucidated. Within the last few years, the discovery of lactylation has propelled the well-known exercise metabolite lactate into the scientific spotlight. As the end product of glycolysis, lactate was initially considered to be a "metabolic waste" leading to muscle fatigue; however, subsequent studies have demonstrated the importance of lactate as an energy substrate and a signal transduction molecule to coordinate various physiological processes. Importantly, the novel posttranslational modification, lactylation, establishes a bridge between lactate and epigenetics, and provides new perspectives for understanding the role of lactate in exercise-mediated health promotion. Although some recent evidence in rodents suggests that exercise increases protein lactylation, there are mixed findings in this area, with limited human studies showing no effects. This review summarizes current knowledge of exercise-mediated lactylation, why mixed findings in the literature may exist, and suggests future research that can add further clarity to this area of molecular biology.