Journal Article

Exercise and Training Regulation of Autophagy Markers in Human and Rat Skeletal Muscle

Lazarou, Michael, Perri, Enrico, Jamnick, Nicholas A., Granata, Cesare, Bishop, David J., Botella, Javier, Genders, Amanda J., Jabar, Tamim, Garnham, Andrew

2022

Overview

Autophagy is a key intracellular mechanism by which cells degrade old or dysfunctional proteins and organelles. In skeletal muscle, evidence suggests that exercise increases autophagosome content and autophagy flux. However, the exercise-induced response seems to differ between rodents and humans, and little is known about how different exercise prescription parameters may affect these results. The present study utilised skeletal muscle samples obtained from four different experimental studies using rats and humans. Here, we show that, following exercise, in the soleus muscle of Wistar rats, there is an increase in LC3B-I protein levels immediately after exercise (+109%), and a subsequent increase in LC3B-II protein levels 3 h into the recovery (+97%), despite no change in Map1lc3b mRNA levels. Conversely, in human skeletal muscle, there is an immediate exercise-induced decrease in LC3B-II protein levels (−24%), independent of whether exercise is performed below or above the maximal lactate steady state, which returns to baseline 3.5 h following recovery, while no change in LC3B-I protein levels or MAP1LC3B mRNA levels is observed. SQSTM1/p62 protein and mRNA levels did not change in either rats or humans following exercise. By employing an ex vivo autophagy flux assay previously used in rodents we demonstrate that the exercise-induced decrease in LC3B-II protein levels in humans does not reflect a decreased autophagy flux. Instead, effect size analyses suggest a modest-to-large increase in autophagy flux following exercise that lasts up to 24 h. Our findings suggest that exercise-induced changes in autophagosome content markers differ between rodents and humans, and that exercise-induced decreases in LC3B-II protein levels do not reflect autophagy flux level.

• Publisher: MDPI AG,MDPI
• Subject: Animals / Autophagy / Autophagy - physiology / Biomarkers - metabolism / Exercise intensity / Fitness training programs / Humans / Microtubule-Associated Proteins - genetics / Microtubule-Associated Proteins - metabolism / Muscle, Skeletal - metabolism / Musculoskeletal system / Physical Conditioning, Animal - physiology / Proteins / Rats / Rats, Wistar / RNA, Messenger - genetics / RNA, Messenger - metabolism / Rodents