Mechanisms for Regulatory Effects of Exercise on Metabolic Diseases from the Lactate-Lactylation Perspective.
Level 5 - mechanism / opinion, no new human data
Narrative mechanistic review with no original clinical data or systematic synthesis.
PubMed 40331975 · doi:10.3390/ijms26083469
What was done
This is a narrative review synthesizing literature on the mechanistic role of lactate and histone/protein lactylation in metabolic diseases—including cardiovascular diseases, type 2 diabetes mellitus, osteoporosis, and non-alcoholic fatty liver disease—and how acute exercise modulates these pathologies via lactylation-dependent pathways.
What was found
The abstract reports no numerical data or effect sizes. It qualitatively describes molecular pathways: chronic hyperlactatemia suppresses mitochondrial biogenesis via epigenetic silencing of oxidative metabolism genes, whereas exercise-induced lactate surges transiently enhance insulin sensitivity via AMPK / PGC-1α / GLUT4 signaling, promote GPR81-mediated M2 macrophage polarization to resolve inflammation, and restore mitochondrial function via lactylation-dependent transcriptional remodeling.
Why it matters
It provides a conceptual framework distinguishing the benefits of transient, exercise-induced lactylation from the pathological consequences of chronic hyperlactatemia across metabolic diseases.
Limits
As a non-systematic narrative review, it presents no original clinical or experimental data, provides no sample sizes, and lacks quantitative synthesis or defined tissue-specific concentration thresholds.
Cited by
- supports Lactate produced during vigorous exercise acts as a signaling molecule that activates PGC-1alpha, a primary regulator of mitochondrial biogenesis.