Skeletal Muscle Fiber Type in Hypoxia: Adaptation to High-Altitude Exposure and Under Conditions of Pathological Hypoxia

Abstract

Skeletal muscle is able to modify its size, and its metabolic/contractile properties in response to a variety of stimuli, such as mechanical stress, neuronal activity, metabolic and hormonal influences, and environmental factors. A reduced oxygen availability, called hypoxia, has been proposed to induce metabolic adaptations and loss of mass in skeletal muscle. In addition, several evidences indicate that muscle fiber-type composition could be affected by hypoxia. The main purpose of this review is to explore the adaptation of skeletal muscle fiber-type composition to exposure to high altitude (ambient hypoxia) and under conditions of pathological hypoxia, including chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) and obstructive sleep apnea syndrome (OSAS). The muscle fiber-type composition of both adult animals and humans is not markedly altered during chronic exposure to high altitude. However, the fast-to-slow fiber-type transition observed in hind limb muscles during post-natal development is impaired in growing rats exposed to severe altitude. A slow-to-fast transition in fiber type is commonly found in lower limb muscles from patients with COPD and CHF, whereas a transition toward a slower fiber-type profile is often found in the diaphragm muscle in these two pathologies. A slow-to-fast transformation in fiber type is generally observed in the upper airway muscles in rodent models of OSAS. The factors potentially responsible for the adaptation of fiber type under these hypoxic conditions are also discussed in this review. The impaired locomotor activity most likely explains the changes in fiber type composition in growing rats exposed to severe altitude. Furthermore, chronic inactivity and muscle deconditioning could result in the slow-to-fast fiber-type conversion in lower limb muscles during COPD and CHF, while the factors responsible for the adaptation of muscle fiber type during OSAS remain hypothetical. Finally, the role played by cellular hypoxia, hypoxia-inducible factor-1 alpha (HIF-1α), and other molecular regulators in the adaptation of muscle fiber-type composition is described in response to high altitude exposure and conditions of pathological hypoxia.

Comparative transcriptomic and metabolomic analysis reveals pectoralis highland adaptation across altitudinal songbirds

“…Therefore, the physiological responses to hypoxic hypothermia of highland are generally found by increasing oxidative capacity as well as oxygen delivery and by altering oxygen utilization in pectoralis [2]. Either size modi cation of muscle ber or myo bril in highland birds plays an important role on heat production through shivering thermogenesis for maintenance of a constant core body temperature [17]. Various modi cations of muscle phenotype across altitudinal birds are probably associated with the ight performance in hypoxic environment for an increased size of myo bril which would produce more contractile force to prevent ightless, probably accounting for why highland tree sparrows perform a weak ight capacity [18].…”

Comparative transcriptomic and metabolomic analysis reveals pectoralis highland adaptation across altitudinal songbirds

“…Therefore, the physiological responses to hypoxic hypothermia of highland are generally found by increasing oxidative capacity as well as oxygen delivery and by altering oxygen utilization in pectoralis [2]. Either size modification of muscle fiber or myofibril in highland birds plays an important role on heat production through shivering thermogenesis for maintenance of a constant core body temperature [17]. Additionally, the ratio of wing length to body length significantly associates with muscle fiber area (R 2 = 0.36, p = 0.0002, Figure S6a) and myofibril diameter (R 2 = 0.51, p < 0.0001, Figure S6b).…”

The secretome of human dental pulp stem cells protects myoblasts from hypoxia‑induced injury via the Wnt/β‑catenin pathway

“…Hypoxia occurs during numerous common phenomena, including embryogenesis, exposure to high-altitude areas, physical exercise and diseases (1,2). Pathological hypoxia can impair skeletal muscle function, a characteristic that it shares with chronic hypoxia-related diseases, such as chronic heart failure (3), chronic obstructive pulmonary disease (4), type 2 diabetes (5) and obstructive sleep apnea syndrome (6,7).…”