Acute normobaric hypoxia blunts contraction‐mediated mTORC1‐ and JNK‐signaling in human skeletal muscle

Abstract

Aim: Hypoxia has been shown to reduce resistance exercise-induced stimulation of protein synthesis and long-term gains in muscle mass. However, the mechanism whereby hypoxia exerts its effect is not clear. Here, we examine the effect of acute hypoxia on the activity of several signalling pathways involved in the regulation of muscle growth following a bout of resistance exercise.Methods: Eight men performed two sessions of leg resistance exercise in normoxia or hypoxia (12% O 2 ) in a randomized crossover fashion. Muscle biopsies were obtained at rest and 0, 90,180 minutes after exercise. Muscle analyses included levels of signalling proteins and metabolites associated with energy turnover.Results: Exercise during normoxia induced a 5-10-fold increase of S6K1 Thr389 phosphorylation throughout the recovery period, but hypoxia blunted the increases by ~50%. Phosphorylation of JNK Thr183/Tyr185 and the JNK target SMAD2 Ser245/250/255 was increased by 30-to 40-fold immediately after the exercise in normoxia, but hypoxia blocked almost 70% of the activation. Throughout recovery, phosphorylation of JNK and SMAD2 remained elevated following the exercise in normoxia, but the effect of hypoxia was lost at 90-180 minutes postexercise. Hypoxia had no effect on exercise-induced Hippo or autophagy signalling and ubiquitin-proteasome related protein levels. Nor did hypoxia alter the changes induced by exercise in high-energy phosphates, glucose 6-P, lactate or phosphorylation of AMPK or ACC. Conclusion:We conclude that acute severe hypoxia inhibits resistance exerciseinduced mTORC1-and JNK signalling in human skeletal muscle, effects that do not appear to be mediated by changes in the degree of metabolic stress in the muscle.

Exercise‐mediated autophagy in cardiovascular diseases

“…15 This process is significantly regulated by autophagy. [16][17][18] An increased autophagic flux was detected in peripheral blood mononuclear cells (PBMC) immediately after acute exercise and persisted for 4 h during the recovery period. 17 Chronic adaptations of the heart are thought to be the major feature of long-term exercise.…”

“…Accordingly, the release of metabolites and other local vasoactive compounds (such as kinins) is increased to control blood flow and meet the increasing energy demand in muscle 15 . This process is significantly regulated by autophagy 16–18 . An increased autophagic flux was detected in peripheral blood mononuclear cells (PBMC) immediately after acute exercise and persisted for 4 h during the recovery period 17 …”

How hypoxia blunts protein synthesis activation after resistance exercise

“…This is the topic of a highly rated manuscript in this issue of Acta Physiologica by Moberg and colleagues from the Swedish School of Sport and Health Sciences. 5 In their study, eight men performed two sessions of leg resistance exercise in Normoxia or Hypoxia (12% O 2 ) in a randomized crossover fashion. Subjects were equipped with a facemask connected to an altitude generator set at normoxia or FiO 2 12%.…”

“…How does severe hypoxia blunt training‐induced increases in protein synthesis in human skeletal muscle? This is the topic of a highly rated manuscript in this issue of Acta Physiologica by Moberg and colleagues from the Swedish School of Sport and Health Sciences 5 . In their study, eight men performed two sessions of leg resistance exercise in Normoxia or Hypoxia (12% O 2 ) in a randomized crossover fashion.…”

Exercise and energy

“…However, the interrelation of ergogenic mechanisms and pathophysiology have been investigated by, 12 showing how the Na/K ATPase regulates metabolic reserve—and susceptibility to Western diet‐related diseases 12,13 . Other interesting studies have focussed on the concepts of (a) fatigability 14 and (b) muscle metabolism at rest and during different levels of use and stress, elucidating both the mechanisms of energy generation and consumption with regard to both physiological function and pathophysiology 15–17 …”