Exercise and exercise training-induced increase in autophagy markers in human skeletal muscle

Abstract

Moderately trained male subjects (mean age 25 years; range 19–33 years) completed an 8‐week exercise training intervention consisting of continuous moderate cycling at 157 ± 20 W for 60 min (MOD; n = 6) or continuous moderate cycling (157 ± 20 W) interspersed by 30‐sec sprints (473 ± 79 W) every 10 min (SPRINT; n = 6) 3 days per week. Sprints were followed by 3:24 min at 102 ± 17 W to match the total work between protocols. A muscle biopsy was obtained before, immediately and 2 h after the first training session as well as at rest after the training session. In both MOD and SPRINT, skeletal muscle AMPKT hr172 and ULKS er317 phosphorylation was elevated immediately after exercise, whereas mTORS er2448 and ULKS er757 phosphorylation was unchanged. Two hours after exercise LC3I, LC3II and BNIP3 protein content was overall higher than before exercise with no change in p62 protein. In MOD, Beclin1 protein content was higher immediately and 2 h after exercise than before exercise, while there were no differences within SPRINT. Oxphos complex I, LC3I, BNIP3 and Parkin protein content was higher after the training intervention than before in both groups, while there was no difference in LC3II and p62 protein. Beclin1 protein content was higher after the exercise training intervention only in MOD. Together this suggests that exercise increases markers of autophagy in human skeletal muscle within the first 2 h of recovery and 8 weeks of exercise training increases the capacity for autophagy and mitophagy regulation. Hence, the present findings provide evidence that exercise and exercise training regulate autophagy in human skeletal muscle and that this in general was unaffected by interspersed sprint bouts.

High‐intensity exercise training ameliorates aberrant expression of markers of mitochondrial turnover but not oxidative damage in skeletal muscle of men with essential hypertension

“…On the other hand, the increase in p62 observed following the training period in both the hypertensive and the normotensive group suggests that the capacity for autophagy regulation increased with exercise training independent of hypertension. Overall, the present findings are in contrast to the unaltered levels of LC3‐II and p62 documented in either healthy young or elderly men following an exercise training period, with such discrepancies possibly related to the different characteristics of the populations and the exercise training interventions employed. It should be noted that even though LC3 and p62 have been widely used as markers of autophagy, they are indicators of the rate of lysosome formation, but not degradation, which would provide a more specific measure of the autophagic flux .…”

Downregulation of miR-26b-5p, miR-204-5p, and miR-497-3p Expression Facilitates Exercise-Induced Physiological Cardiac Hypertrophy by Augmenting Autophagy in Rats

“…Physical exercise has been identified as an inducer of autophagy (Halling and Pilegaard, 2017;Martin-Rincon et al, 2018). Exercise was reported to induce autophagy in several organs such as cardiac tissue, skeletal muscle, liver, pancreas, hippocampus, and adipose tissue (Brandt et al, 2018;Li et al, 2018b). Induction of skeletal and cardiac muscle autophagy during endurance training triggers beneficial adaptive changes in mitochondrial metabolism and is associated with enhanced physical fitness (Lira et al, 2013).…”

Mitophagy Regulation in Skeletal Muscle: Effect of Endurance Exercise and Age

“…Chronic exercise training is known to induce long-term biochemical and morphological adaptations. These alterations include enhanced mitochondrial content brought upon by changes in both mitochondrial biogenesis and mitophagy [3,43]. Ju et al [24] and Lira et al [34] have found an increase in autophagy and mitophagy markers with exercise training.…”

“…These increases were likely due to transient Ca 2+ fluxes and subsequent calcineurin activation, since inhibition of calcineurin prevented TFEB translocation to the nucleus. Another mechanism that may be involved in the contractile activity induced increase in AMPK phosphorylation, which can negatively regulate mTORC1 function [3,23]. This inactivation of mTORC1 may reduce TFEB phosphorylation, thereby promoting its nuclear localization, an effect that was not apparent in PGC-1α KO mice, suggesting an additional role for PGC-1α as an enhancer of TFEB-mediated autophagic induction [12].…”