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

G Chen,

Jinchao Liu,

Yongbin Guo

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3469 - 3469

Опубликована: Апрель 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.

Язык: Английский

Iron chelators loaded on myocardiocyte mitochondria-targeted nanozyme system for treating myocardial ischemia-reperfusion injury in mouse models DOI Creative Commons
Ke Zhu, Kun Wang,

Rongting Zhang

и другие.

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 15, 2025

Ferroptosis plays a critical role in myocardial ischemia-reperfusion injury (MIRI), posing significant clinical challenge. Nanoenzymes like cerium oxide (CeO2) hold promise for mitigating oxidative damage and inhibiting ferroptosis, but their delivery efficiency biological activity require optimization. This study aims to develop targeted nanozyme system MIRI treatment by integrating CeO2 with mesoporous polydopamine (mPDA) dexrazoxane (DXZ) achieve synergistic therapeutic effects. A biomineralization technique was used synthesize nanoparticles (2–3 nm) within mPDA, forming ~ 130 nm composite (Ce@mPDA). Surface modifications cardiac homing peptide (CHP) triphenylphosphine (TPP) enabled hierarchical targeting injured myocardium mitochondria. DXZ-loaded Ce@mPDA-C/P (D/Ce@mPDA-C/P) were evaluated vitro mouse model effects on stress, apoptosis, inflammation, function. D/Ce@mPDA-C/P exhibited robust ROS scavenging, sustained DXZ release, efficient mitochondrial targeting. The significantly reduced upregulated GPX4 expression, inhibited modulated the inflammatory microenvironment. Long-term studies demonstrated reductions fibrosis improvements function, including enhanced fractional shortening ejection fraction. effectively combines antioxidant properties of iron-chelating DXZ, providing promising strategy MIRI. approach may expand use advance nanomedicine-based interventions repair.

Язык: Английский

Процитировано

1
Turning sour into sweet: Lactylation modification as a promising target in cardiovascular health DOI

Yajie Liao,

Liyan Niu,

Jitao Ling

и другие.

Metabolism, Год журнала: 2025, Номер unknown, С. 156234 - 156234

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Mechanisms for Regulatory Effects of Exercise on Metabolic Diseases from the Lactate–Lactylation Perspective DOI Open Access

G Chen,

Jinchao Liu,

Yongbin Guo

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3469 - 3469

Опубликована: Апрель 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.

Язык: Английский

Процитировано

0