title: Activation of autophagy in human skeletal muscle is dependent on exercise intensity and AMPK activation.
abstract: In humans, nutrient deprivation and extreme endurance exercise both activate autophagy. We hypothesized that cumulating fasting and cycling exercise would potentiate activation of autophagy in skeletal muscle. Well-trained athletes were divided into control (n = 8), low-intensity (LI, n = 8), and high-intensity (HI, n = 7) exercise groups and submitted to fed and fasting sessions. Muscle biopsy samples were obtained from the vastus lateralis before, at the end, and 1 h after a 2 h LI or HI bout of exercise. Phosphorylation of ULK1(Ser317) was higher after exercise (P < 0.001). In both the fed and the fasted states, LC3bII protein level and LC3bII/I were decreased after LI and HI (P < 0.05), while p62/SQSTM1 was decreased only 1 h after HI (P < 0.05), indicating an increased autophagic flux after HI. The autophagic transcriptional program was also activated, as evidenced by the increased level of LC3b, p62/SQSTM1, GabarapL1, and Cathepsin L mRNAs observed after HI but not after LI. The increased autophagic flux after HI exercise could be due to increased AMP-activated protein kinase α (AMPKα) activity, as both AMPKα(Thr172) and ACC(Ser79) had a higher phosphorylation state after HI (P < 0.001). In summary, the most effective strategy to activate autophagy in human skeletal muscle seems to rely on exercise intensity more than diet.
authors.affiliation: *Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium; and Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Leuven, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Schwalm
authors.affiliation: *Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium; and Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Leuven, Belgium.
authors.forename: Cécile
authors.initials: C
authors.lastname: Jamart
authors.affiliation: *Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium; and Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Leuven, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Benoit
authors.affiliation: *Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium; and Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Leuven, Belgium.
authors.forename: Damien
authors.initials: D
authors.lastname: Naslain
authors.affiliation: *Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium; and Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Prémont
authors.affiliation: *Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium; and Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Leuven, Belgium.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Prévet
authors.affiliation: *Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium; and Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Leuven, Belgium.
authors.forename: Ruud
authors.initials: R
authors.lastname: Van Thienen
authors.affiliation: *Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium; and Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Leuven, Belgium.
authors.forename: Louise
authors.initials: L
authors.lastname: Deldicque
authors.affiliation: *Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium; and Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Leuven, Belgium marc.francaux@uclouvain.be.
authors.forename: Marc
authors.initials: M
authors.lastname: Francaux
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D056668:Cathepsin L / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005215:Fasting / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D010807:Physical Endurance / Q000502:physiology; D052097:Quadriceps Muscle / Q000378:metabolism* / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C430503:GABARAPL1 protein, human; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D055372:AMP-Activated Protein Kinases; C534281:CTSL protein, human; D056668:Cathepsin L
keywords: LC3b; cathepsin; cycling; fasting; p62/SQSTM1