Lactylation in metabolic dysfunction-associated steatotic liver disease: epigenetic regulatory mechanisms and potential therapeutic strategies.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease characterized by metabolic dysfunction as the central feature, and its onset and progression are closely associated with insulin resistance and energy metabolism reprogramming. Traditionally, lactate has been considered mainly as a metabolic byproduct generated during glycolysis. Recent studies, however, have indicated that lactate can also act as an important metabolic source for lysine lactylation modification, and it participates in the regulation of cellular metabolism. In the liver, lactylation can participate in the progression of MASLD by affecting multiple pathological processes, including lipid metabolism, inflammatory responses, and fibrosis. In addition, lactylation modification exhibits a dual regulatory role in MASLD, with both pro-pathological and protective effects. Intervention strategies targeting lactate metabolism and lactylation have gradually become an important direction in MASLD therapeutic research. This article systematically reviews the mechanisms of lactylation modification in MASLD as well as the research progress and translational limitations of related intervention strategies, aiming to provide a theoretical reference for the development of potential therapeutic targets for MASLD.