PGC-1αpromotes exercise-induced autophagy in mouse skeletal muscle

Abstract

Recent evidence suggests that exercise stimulates the degradation of cellular components in skeletal muscle through activation of autophagy, but the time course of the autophagy response during recovery from exercise has not been determined. Furthermore, the regulatory mechanisms behind exercise‐induced autophagy remain unclear, although the muscle oxidative phenotype has been linked with basal autophagy levels. Therefore, the aim of this study was to investigate the role of the key regulator of muscle oxidative capacity, PGC‐1α, in exercise‐induced autophagy at several time points during recovery. Mice with transgenic muscle‐specific overexpression (TG) or knockout (MKO) of PGC‐1α and their respective littermate controls were subjected to a single 1 h bout of treadmill running and euthanized immediately (0 h), 2, 6, and 10 h after exercise. In the PGC‐1α MKO strain, quadriceps protein content of the autophagy marker LC3II was increased from 2 h into recovery in lox/lox control, but not in MKO mice. In the PGC‐1α TG strain, quadriceps protein content of LC3II was increased from 2 h after exercise in TG, but not in WT. Although AMPK and ACC phosphorylation was increased immediately following exercise, the observed exercise‐induced autophagy response was not associated with phosphorylation of the AMPK‐target ULK1. However, lower protein carbonyl content was observed in lox/lox and TG mice after exercise coinciding with the increased LC3 lipidation. In conclusion, the present results suggest a role of skeletal muscle PGC‐1α in coordinating several exercise‐induced adaptive responses including autophagic removal of damaged cellular components.

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

“…; Halling et al. ; Brandt et al. ) and in part with a previous study in humans showing an increase in LC3b mRNA content in skeletal muscle in response to acute ultra‐endurance running (Jamart et al.…”

“…; Halling et al. ). Moreover, previous mouse studies have shown an increase in LC3II protein in response to an acute bout of endurance exercise (Grumati et al.…”

“…; Halling et al. ; Brandt et al. ), whereas the response in human skeletal muscle may be more complex.…”

Muscle PGC‐1α in exercise and fasting‐induced regulation of hepatic UPR in mice

“…22 Littermate TG and wild-type (WT) mice were obtained by crossing heterozygous TG mice with WT mice and the genotype was determined by PCR as previously described. 20 In addition, unpublished data from our group show that there is no significant difference in PGC-1α mRNA in liver, visceral and subcutaneous adipose tissue between WT and TG mice, supporting muscle-specific PGC-1α overexpression. 20 In addition, unpublished data from our group show that there is no significant difference in PGC-1α mRNA in liver, visceral and subcutaneous adipose tissue between WT and TG mice, supporting muscle-specific PGC-1α overexpression.…”

“…The present observation that PERK, eIF2α and IRE1α phosphorylation decreased with fasting may be an indication of energy sparing of the liver. 20 However, future studies are needed to clarify the role of autophagy in the liver. However, the observation that several other downstream UPR mRNAs increased with fasting indicates that UPR was activated in response to fasting and is in line with the observed increase in cleaved ATF6 protein in the current study.…”