Resistance training in humans and mechanical overload in rodents do not elevate muscle protein lactylation

Authors

Madison L. Mattingly, Auburn University
Auburn University A. Ruple, Auburn University
Casey L. Sexton, University of Florida
Joshua S. Godwin, Auburn University
Mason C. McIntosh, Auburn University
Morgan A. Smith, Standford University
Daniel L. Plotkin, Auburn University
J. Max Michel, Auburn University
Derick A. Anglin, Auburn University
Nicholas J. Kontos, Auburn University
Shengyi Fei, University of Nebraska- Lincoln
Stuart M. Phillips, McMaster University
C. Brooks Mobley, Auburn University
Ivan Jose Vechetti Jr, University of Nebraska-LincolnFollow
Christopher G. Vann, Duke University
Michael D. Roberts, Auburn University

Document Type

Article

Date of this Version

9-28-2023

Citation

Mattingly ML, Ruple BA, Sexton CL, Godwin JS, McIntosh MC, Smith MA, Plotkin DL, Michel JM, Anglin DA, Kontos NJ, Fei S, Phillips SM, Mobley CB, Vechetti I, Vann CG and Roberts MD (2023), Resistance training in humans and mechanical overload in rodents do not elevate muscle protein lactylation. Front. Physiol. 14:1281702. doi: 10.3389/fphys.2023.1281702

Comments

Open access.

Abstract

Although several reports have hypothesized that exercise may increase skeletal muscle protein lactylation, empirical evidence in humans is lacking. Thus, we adopted a multifaceted approach to examine if acute and subchronic resistance training (RT) altered skeletal muscle protein lactylation levels. In mice, we also sought to examine if surgical ablation-induced plantaris hypertrophy coincided with increases in muscle protein lactylation. To examine acute responses, participants’ blood lactate concentrations were assessed before, during, and after eight sets of an exhaustive lower body RT bout (n = 10 trained college-aged men). Vastus lateralis biopsies were also taken before, 3-h post, and 6-h post-exercise to assess muscle protein lactylation. To identify training responses, another cohort of trained college-aged men (n = 14) partook in 6 weeks of lower-body RT (3x/week) and biopsies were obtained before and following the intervention. Five-month-old C57BL/6 mice were subjected to 10 days of plantaris overload (OV, n = 8) or served as age-matched sham surgery controls (Sham, n = 8). Although acute resistance training significantly increased blood lactate responses ~7.2- fold (p < 0.001), cytoplasmic and nuclear protein lactylation levels were not significantly altered at the post-exercise time points, and no putative lactylation-dependent mRNA was altered following exercise. Six weeks of RT did not alter cytoplasmic protein lactylation (p = 0.800) despite significantly increasing VL muscle size (+3.5%, p=0.037), and again, no putative lactylation-dependent mRNA was significantly affected by training. Plantaris muscles were larger in OV versus Sham mice (+43.7%, p < 0.001). However, cytoplasmic protein lactylation was similar between groups (p = 0.369), and nuclear protein lactylation was significantly lower in OV versus Sham mice (p < 0.001). The current null findings, along with other recent null findings in the literature, challenge the thesis that lactate has an appreciable role in promoting skeletal muscle hypertrophy.