Schwalm Céline, Jamart Cécile, Benoit Nicolas, Naslain Damien, Prémont Christophe, Prévet Jérémy, Van Thienen Ruud, Deldicque Louise, Francaux Marc
*Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium; and Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Leuven, Belgium.
*Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium; and Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Leuven, Belgium
FASEB J. 2015 Aug;29(8):3515-26. doi: 10.1096/fj.14-267187. Epub 2015 May 8.
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.
在人类中，营养剥夺和极限耐力运动都会激活自噬。我们假设累积禁食和循环运动将增强骨骼肌中自噬的激活。将训练有素的运动员分为对照组（n = 8）、低强度（LI，n = 8）和高强度（HI，n = 7）运动组，并进行进食和禁食训练。在进行2小时的低强度或高强度运动之前、结束时以及结束后1小时，从股外侧肌获取肌肉活检样本。运动后ULK1（Ser317）的磷酸化水平更高（P < 0.001）。在进食和禁食状态下，低强度和高强度运动后LC3bII蛋白水平和LC3bII/I均降低（P < 0.05），而p62/SQSTM1仅在高强度运动后1小时降低（P < 0.05），表明高强度运动后自噬通量增加。自噬转录程序也被激活，高强度运动后观察到LC3b、p62/SQSTM1、GabarapL1和组织蛋白酶L的mRNA水平升高，但低强度运动后未观察到，这证明了这一点。高强度运动后自噬通量增加可能是由于AMP激活的蛋白激酶α（AMPKα）活性增加，因为高强度运动后AMPKα（Thr172）和ACC（Ser79）都具有更高的磷酸化状态（P < 0.001）。总之，激活人类骨骼肌自噬的最有效策略似乎更多地依赖于运动强度而非饮食。
