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

Summary

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.

Conditions

• Exercise
• Hypoxia
• Satellite Cells
• Myogenesis

Interventions

DEVICE

Resistance exercise on an isokinetic dynamometer

Leg flexion/extension: 5 series of 15 repetitions at 60°/sec for the knee extension and 30°/sec for the knee flexion

PROCEDURE

Vastus lateralis biopsy

Biopsy taken in the vastus lateralis

PROCEDURE

Blood samples

Blood samples taken from the antecubital vein

DEVICE

Normoxia

Environmental condition for exercise: in a pressurized chamber with a inspired oxygen fraction of 0.21 (sea level)

DEVICE

Hypoxia

Environmental hypoxia: in a chamber where oxygen is extracted and replaced by nitrogen to reach an inspired oxygen fraction of 0.135 (equivalent to 2500m altitude)

DEVICE

Blood flow restriction

Tourniquet placed around the proximal extremity of the lower limb and inflated at 60% of arterial occlusion pressure to induce local hypoxia

Sponsors & Collaborators

• Université Catholique de Louvain

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

49 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-04-04

Primary Completion

2023-05-08

Completion

2025-09-05

Countries

• Belgium

Study Locations