Protein Lactylation in Liver Disease: A Comprehensive Review.

Abstract

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Lactate, generated through glycolysis, plays a dual role as both a metabolic substrate and a signalling molecule, influencing cellular functions in pathophysiological scenarios. Protein lactylation, a recently identified form of post-translational modification mediated by lactate, has garnered significant and increasing attention. Globally, hepatic disorders pose a significant public health burden, frequently involving disruptions in glucose metabolism and consequent lactate buildup. This comprehensive review examines the discovery, regulatory mechanisms and pathogenic roles of lactylation in diverse liver disorders, while critically evaluating emerging lactylation-targeted therapeutics to guide future translational research. Lactylation modifications play a pivotal role in various pathophysiological processes, including hepatic inflammation, liver fibrosis, ischaemic injury, tumour growth and metastasis. Modulation of lactylation pathways, coupled with pharmacological control of lactate synthesis and shuttling, emerges as a strategic approach to liver disease therapeutics.