Regulation of Satellite Cells and Myogenesis in Response to Eccentric Resistance Exercise in Hypoxia

Satellite cells (SC) are muscle stem cells that once activated, proliferate, and differentiate into myocytes that finally fuse with an existing myofiber to regenerate or increase its mass. This process is called 'myogenesis'. Satellite cell activation can be modulated by exercise and by hypoxia. Hypoxia is a state of lower availability of oxygen that can be reached either by going at high altitude (hypobaric hypoxia) or by lowering the percentage of oxygen in hypoxic rooms at sea level. In opposition to the previously described systemic hypoxia, local hypoxia can be reached placing a cuff around a limb, which will induce a partial vascular occlusion. The latter is termed as blood flow restriction (BFR). In addition, in response to physical exercise, a local intramuscular hypoxia can be found back in the skeletal muscle. Myogenesis has been shown to be modulated by hypoxia in different ways, depending on the level of hypoxia: in conditions of mild hypoxia, satellite cell proliferation appears to be favorized, whereas SC differentiation is decreased in those conditions. In conditions of severe hypoxia, SC quiescence is promoted. SC activation increases in response to resistance training, with and without BFR. Some recent data also suggest that resistance exercise in hypoxic rooms may modulate SC activation, but this area is less well understood. Eccentric exercise may enhance SC activation in comparison to concentric contraction. Up to now, no study has analyzed SC activation and myogenesis in response to an eccentric exercise in hypoxia. Whereas macroscopic differences such as higher muscle force gains or hypertrophy, have been observed between normoxic and hypoxic resistance training, but could not be explained by the classical protein balance and growth factors, there is a need for a better understanding of the muscle response in hypoxia and several studies suggest a role of satellite cells and myogenesis in that difference. The purpose of this study is to elucidate whether or not satellite cells are regulated in a different way in response to an eccentric exercise in hypoxia comparing to normoxia. In addition, differences in SC activation between environmental normobaric hypoxia and BFR, two methods used to reach hypoxia at sea level, are not well understood yet. Finally, most of the studies evaluating myogenic response following a resistance exercise have only taken samples at two time-points, before and 24h after exercise in most of the cases. As the different steps of the myogenic process evolves over the days and may be enhanced or inhibited by hypoxic conditions, multiple time-points would be interesting to observe the evolution of the myogenic process. In that purpose, blood and skeletal muscle samples will be taken at different time-points to evaluate the progress of myogenesis following an acute eccentric exercise. Myogenic regulatory factors will be analyzed by RT-qPCR (mRNA), Western-Blot (protein) and immunofluorescence (localization). In addition, factors able to regulate myogenesis such as muscle damage, inflammation, growth factors, early-regulated genes, MAPK… will also be analyzed in order to understand if they play a role in response to hypoxic conditions.