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J Appl Physiol (1985). 2018 Nov 1;125(5):1609-1619. doi: 10.1152/japplphysiol.01146.2017. Epub 2018 Aug 30.

Training state and skeletal muscle autophagy in response to 36 h of fasting.

Author information

1
Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen , Copenhagen , Denmark.
2
Section of Integrative Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen , Copenhagen , Denmark.
3
Clinical Metabolomics Core Facility, Department of Clinical Biochemistry, Rigshospitalet, Department of Biomedical Sciences, University of Copenhagen , Copenhagen , Denmark.
4
Department of Clinical Biochemistry, Centre of Inflammation and Metabolism, and Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen , Copenhagen , Denmark.

Abstract

The present study aimed at investigating fasting-induced responses in regulators and markers of autophagy in vastus lateralis muscle from untrained and trained human subjects. Untrained and trained subjects (based on maximum oxygen uptake, muscle citrate synthase activity, and oxidative phosphorylation protein level) fasted for 36 h with vastus lateralis muscle biopsies obtained at 2, 12, 24, and 36 h after a standardized meal. Fasting reduced ( P < 0.05) skeletal muscle microtubule-associated protein-1A/1B light chain 3 (LC3)I, LC3II, and adaptor protein sequestosome 1/p62 protein content in untrained subjects only. Moreover, skeletal muscle RAC-alpha serine/threonine-protein kinase (AKT)Thr308, AMP-activated protein kinase (AMPK)Thr172, and Unc-51-like autophagy-activating kinase-1 (ULK1)Ser555 phosphorylation state, as well as Bcl-2-interacting coiled-coil protein-1 (Beclin1) and ULK1Ser757 phosphorylation, was lower ( P < 0.05) in trained than untrained subjects during fasting. In addition, the plasma concentrations of several amino acids were higher ( P < 0.05) in trained than untrained subjects, and the plasma concentration profile of several amino acids was different in untrained and trained subjects during fasting. Taken together, these findings suggest that 36-h fasting has effects on some mediators of autophagy in untrained human skeletal muscle and that training state influences the effect of fasting on autophagy signaling and on mediators of autophagy in skeletal muscle. NEW & NOTEWORTHY This study showed that skeletal muscle autophagy was only modestly affected in humans by 36 h of fasting. Hence, 36-h fasting has effects on some mediators of autophagy in untrained human skeletal muscle, and training state influences the effect of fasting on autophagy signaling and on mediators of autophagy in skeletal muscle.

KEYWORDS:

autophagy; exercise training; fasting; plasma amino acid; signaling; skeletal muscle

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