Mechanisms for Regulatory Effects of Exercise on Metabolic Diseases from the Lactate–Lactylation Perspective DOI Open Access

G Chen,

Jinchao Liu,

Yongbin Guo

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3469 - 3469

Published: April 8, 2025

Metabolic diseases, including cardiovascular type 2 diabetes mellitus (T2DM), osteoporosis, and non-alcoholic fatty liver disease (NAFLD), constitute a major global health burden associated with chronic morbidity mortality. Lactate, once considered as metabolic byproduct, has emerged key regulator of cellular reprogramming through lactylation, novel post-translational modification (PTM) that dynamically couples flux to chromatin remodeling. Lactylation exerts dual regulatory roles signaling molecule via GPR81/GPR4-mediated pathways substrate for the covalent histones enzymes. Pathologically, hyperlactatemia suppresses mitochondrial biogenesis, driving cardiomyopathy epigenetic silencing oxidative metabolism genes. Conversely, exercise-induced lactate surges transiently enhance insulin sensitivity AMPK/PGC-1α/GLUT4 signaling, resolve inflammation GPR81-mediated M2 macrophage polarization, restore function lactylation-dependent pathways. This review delineates lactylation spatiotemporal rheostat: dysregulation perpetuates disorders, whereas acute exercise-mediated remodels transcriptional networks homeostasis. Future research should integrate multiomics clarify lactylation’s dynamics, tissue-specific thresholds, metabolism–immunity interactions, metabolic–epigenetic crosstalk precision management diseases.

Language: Английский

Mechanisms for Regulatory Effects of Exercise on Metabolic Diseases from the Lactate–Lactylation Perspective DOI Open Access

G Chen,

Jinchao Liu,

Yongbin Guo

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3469 - 3469

Published: April 8, 2025

Metabolic diseases, including cardiovascular type 2 diabetes mellitus (T2DM), osteoporosis, and non-alcoholic fatty liver disease (NAFLD), constitute a major global health burden associated with chronic morbidity mortality. Lactate, once considered as metabolic byproduct, has emerged key regulator of cellular reprogramming through lactylation, novel post-translational modification (PTM) that dynamically couples flux to chromatin remodeling. Lactylation exerts dual regulatory roles signaling molecule via GPR81/GPR4-mediated pathways substrate for the covalent histones enzymes. Pathologically, hyperlactatemia suppresses mitochondrial biogenesis, driving cardiomyopathy epigenetic silencing oxidative metabolism genes. Conversely, exercise-induced lactate surges transiently enhance insulin sensitivity AMPK/PGC-1α/GLUT4 signaling, resolve inflammation GPR81-mediated M2 macrophage polarization, restore function lactylation-dependent pathways. This review delineates lactylation spatiotemporal rheostat: dysregulation perpetuates disorders, whereas acute exercise-mediated remodels transcriptional networks homeostasis. Future research should integrate multiomics clarify lactylation’s dynamics, tissue-specific thresholds, metabolism–immunity interactions, metabolic–epigenetic crosstalk precision management diseases.

Language: Английский

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