# Progress of Research on the Metabolic Regulation of Lactylation in Muscle Tissues and Its Disease Associations

## TL;DR

Lactylation connects metabolism and gene regulation in muscles, affecting health and disease, and could lead to new treatments for muscle disorders.

## Contribution

This paper highlights lactylation's role in muscle metabolism and disease, emphasizing its potential as a therapeutic target.

## Key findings

- Lactylation regulates myocyte energy metabolism and exercise adaptation through a dynamic mechanism.
- Aberrant lactylation contributes to insulin resistance and diabetic cardiomyopathy.
- Lactylation has dual effects in cardiovascular diseases, both protecting and aggravating injury.

## Abstract

Lactylation serves as a vital link between cellular metabolism and epigenetic regulation and plays a pivotal role in muscle biology. Muscle tissue is the primary site of lactate production; its unique metabolic environment confers dynamism, specificity and functional diversity for lactylation. Under physiological conditions, lactylation regulates myocyte energy metabolism, proliferation, differentiation, and exercise adaptation through a dynamic “writer–eraser–reader” mechanism. In pathological states, lactate imbalance directly contributes to the progression of various muscular disorders. For instance, diminished histone lactylation during muscle aging suppresses the expression of genes critical for DNA repair and protein homeostasis. Aberrant lactylation is involved in the development of insulin resistance and diabetic cardiomyopathy. Furthermore, lactylation exerts dual effects in cardiovascular diseases; it provides protection by enhancing the transcription of repair genes and simultaneously aggravates injury by promoting processes such as fibrosis and ferroptosis. Collectively, these findings underscore the importance of lactylation in muscular pathologies and provide a theoretical foundation for the development of therapies that target this modification process. As the regulatory mechanisms of lactylation have become clearer, precise interventions targeting specific modification sites are expected to open new therapeutic avenues for muscular diseases.