Author(s): GRIMANDI, L., MURRI, A., FANTINI, C., SIRENO, L., SILVESTRI, M., SGRÒ, P., PARISI, A., CAPOROSSI, D., Institution: UNIVERSITY OF ROME , Country: ITALY, Abstract-ID: 1657

INTRODUCTION:
Lactylation, similar to acetylation, is a novel post-translational modification (PTM) involving the addition of a lactyl group to lysine residues, potentially linking metabolism to protein function and epigenetic regulation. It has been mainly studied in tumor models, while its in vivo modulation under physiological conditions and its dependence on individual characteristics remains unexplored. This study aims to quantify lactylation and acetylation PTMs in global protein and H3 (H3K18) histone in peripheral blood mononuclear cells (PBMCs) from healthy males after an incremental cycling test to exhaustion, controlling for their training status.
METHODS:
Participants (n=10, healthy men aged 25–35; 5 untrained vs. 5 trained) were subjected to an incremental cycling test to exhaustion (8–12 min) with HRmax, VO2max, RCP, and AT assessments. PBMCs have been isolated from fasting blood samples collected before (T0), after 1 hour (T1), and 24 hours (T2) from the exercise. Anthropometric measurements were collected at T0, while plasma lactate was measured pre/post incremental test. Global protein lactylation, acetylation and carbonylation, as well as H3K18 lactylation and acetylation have been analysed via immunoblot. Statistical analysis evaluates pre- and post-exercise changes and intergroup differences.
RESULTS:
Significant differences were observed between trained (TG) and untrained (UG) groups in both VO₂max (P<0.033) and test duration (P<0.011). Plasma lactate increase post-exercise was 13,27+ 3,38, with no group differences. Significant intergroup changes were detected on H3K18 acetylation (P<0.0008) and lactylation (P<0.0137), where TG values were higher than the UG group, but no statistical differences were observed pre/post exercise, nor within or between groups. Significant carbonylation (P<0.0198) differences were found between the two groups, where UG values were higher than those of the TG group, especially after exercise. No significant changes were detected in global protein lactylation, acetylation, or in the expression/phosphorylation of specific target proteins (SOD1, SOD2, HSP27, etc.).
CONCLUSION:
This study investigates lactylation as a novel PTMs marker in exercise biology, alongside with acetylation and irreversible oxidation. Indeed, our findings show that both H3K18 lactylation and acetylation are modulated by chronic physical activity exposure. As expected, training determines a more efficient mechanism to counteract oxidative stress. Ongoing gene expression analyses (p300 and HDAC2) promise to clarify how exercise might modify H3K18 PTMs and its putative role in exercise-induced epigenetic control of immune response.