Regulation of autophagy in human skeletal muscle: effects of exercise, exercise training and insulin stimulation
Research output: Contribution to journal › Journal article › Research › peer-review
Studies in rodent muscle suggest that autophagy is regulated by acute exercise, exercise training and insulin stimulation. However, little is known about the regulation of autophagy in human skeletal muscle. Here we investigate the autophagic response to acute one-legged exercise, one-legged exercise training as well as in response to subsequent insulin stimulation in exercised and non-exercised human muscle. Acute one-legged exercise decreased (p<0.01) lipidation of LC3 (∼50 %) and the LC3-II/LC3-I ratio (∼60 %) indicating that content of autophagosomes decreases with exercise in human muscle. The decrease in LC3-II/LC3-I ratio did not correlate with activation of AMPK trimer complexes in human muscle. Consistently, pharmacological AMPK activation with AICAR in mouse muscle did not affect the LC3-II/LC3-I ratio. Four hours after exercise, insulin further reduced (p<0.01) the LC3-II/LC3-I ratio (∼80%) in muscle of the exercised and non-exercised leg in man. This coincided with increased Ser-757 phosphorylation of ULK1, which is suggested as an mTORC1 target. Accordingly, inhibition of mTOR signalling in mouse muscle prevented the ability of insulin to reduce the LC3-II/LC3-I ratio. In response to 3 weeks of one-legged exercise training, the LC3-II/LC3-I ratio decreased (p<0.05) in both trained and untrained muscle and this change was largely driven by an increase in LC3-I content. Taken together, insulin stimulation and acute exercise reduces muscle autophagosome content, while exercise training may increase the capacity for formation of autophagosomes in muscle. Moreover, AMPK activation during exercise may not be sufficient to regulate autophagy in muscle, while mTORC1 signalling via ULK1 likely mediates the autophagy-inhibiting effect of insulin. This article is protected by copyright. All rights reserved.
|Journal||Journal of Physiology|
|Number of pages||17|
|Publication status||Published - 2016|