High-Intensity Interval Training Induces Protein Lactylation in Different Tissues of Mice with Specificity and Time Dependence

Protein lysine lactylation (Kla) is a novel protein acylation reported in recent years, which plays an important role in the development of several diseases with pathologically elevated lactate levels, such as tumors. The concentration of lactate as a donor is directly related to the Kla level. High-intensity interval training (HIIT) is a workout pattern that has positive effects in many metabolic diseases, but the mechanisms by which HIIT promotes health are not yet clear. Lactate is the main metabolite of HIIT, and it is unknown as to whether high lactate during HIIT can induce changes in Kla levels, as well as whether Kla levels differ in different tissues and how time-dependent Kla levels are. In this study, we observed the specificity and time-dependent effects of a single HIIT on the regulation of Kla in mouse tissues. In addition, we aimed to select tissues with high Kla specificity and obvious time dependence for lactylation quantitative omics and analyze the possible biological targets of HIIT-induced Kla regulation. A single HIIT induces Kla in tissues with high lactate uptake and metabolism, such as iWAT, BAT, soleus muscle and liver proteins, and Kla levels peak at 24 h after HIIT and return to steady state at 72 h. Kla proteins in iWAT may affect pathways related to glycolipid metabolism and are highly associated with de novo synthesis. It is speculated that the changes in energy expenditure, lipolytic effects and metabolic characteristics during the recovery period after HIIT may be related to the regulation of Kla in iWAT.

Automated summary

Protein lysine lactylation (Kla) is a recently reported protein acylation involved in the development of diseases like tumors with elevated lactate levels. This study investigates the effects of high-intensity interval training (HIIT) on Kla regulation in mouse tissues. A single session of HIIT induces Kla in tissues with high lactate uptake and metabolism, reaching peak levels at 24 hours and returning to steady state at 72 hours after the workout. Kla proteins in iWAT may affect glycolipid metabolism pathways and the de novo synthesis process.