Altitude acclimatization and energy metabolic adaptations in skeletal muscle during exercise

Green, H. J.; Sutton, John R.; Wolfel, Eugene E.; Reeves, John Τ.; Butterfield, Gail E.; Brooks, George A.

doi:10.1152/jappl.1992.73.6.2701

Cited by 85 publications

(84 citation statements)

References 19 publications

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“…Yet, lactate concentration and lactate-to-pyruvate ratio were not elevated in the vastus lateralis of subjects exposed for either 4 h or 3 weeks at 4300 m [54,55], while lactate accumulation was increased in the media of C2C12 myotubes 96 h after treatment with PHD inhibitor [35]. Skeletal muscle lactate efflux is notably mediated by MCT4, a monocarboxylate transporter that is upregulated during in vitro hypoxia in a HIF-1-dependent manner [56].…”

Section: Hypoxia-mediated Regulation Of Metabolic Pathwaysmentioning

confidence: 99%

HIF-1-driven skeletal muscle adaptations to chronic hypoxia: molecular insights into muscle physiology

Favier

Britto

Freyssenet

et al. 2015

Cell. Mol. Life Sci.

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Skeletal muscle is a metabolically active tissue and the major body protein reservoir. Drop in ambient oxygen pressure likely results in a decrease in muscle cells oxygenation, reactive oxygen species (ROS) overproduction and stabilization of the oxygen-sensitive hypoxia-inducible factor (HIF)-1α. However, skeletal muscle seems to be quite resistant to hypoxia compared to other organs, probably because it is accustomed to hypoxic episodes during physical exercise. Few studies have observed HIF-1α accumulation in skeletal muscle during ambient hypoxia probably because of its transient stabilization. Nevertheless, skeletal muscle presents adaptations to hypoxia that fit with HIF-1 activation, although the exact contribution of HIF-2, I kappa B kinase and activating transcription factors, all potentially activated by hypoxia, needs to be determined. Metabolic alterations result in the inhibition of fatty acid oxidation, while activation of anaerobic glycolysis is less evident. Hypoxia causes mitochondrial remodeling and enhanced mitophagy that ultimately lead to a decrease in ROS production, and this acclimatization in turn contributes to HIF-1α destabilization. Likewise, hypoxia has structural consequences with muscle fiber atrophy due to mTOR-dependent inhibition of protein synthesis and transient activation of proteolysis. The decrease in muscle fiber area improves oxygen diffusion into muscle cells, while inhibition of protein synthesis, an ATP-consuming process, and reduction in muscle mass decreases energy demand. Amino acids released from muscle cells may also have protective and metabolic effects. Collectively, these results demonstrate that skeletal muscle copes with the energetic challenge imposed by O2 rarefaction via metabolic optimization.

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Section: Hypoxia-mediated Regulation Of Metabolic Pathwaysmentioning

confidence: 99%

HIF-1-driven skeletal muscle adaptations to chronic hypoxia: molecular insights into muscle physiology

Favier

Britto

Freyssenet

et al. 2015

Cell. Mol. Life Sci.

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“…It may be that hypoxia induces a substrate switch from fatty acids to carbohydrate oxidation, since complete oxidation of carbohydrates provides 8 -11% more ATP per mole of oxygen than fatty acid oxidation (16). Meanwhile, a significant loss of skeletal muscle mass and mitochondrial density in hypoxia (9,14) might be considered an adaptive modification decreasing the tissue's demand for limited O 2 and lowering the production of potentially harmful reactive oxygen species (ROS) (13). Changes in cardiac mitochondrial function have recently been described in the hypoxiaacclimatized rat heart (15); however, little is known about skeletal muscle metabolism following acclimatization and the shorter-term metabolic response to hypoxia of both heart and skeletal muscle remains unknown.…”

mentioning

confidence: 99%

Tissue-specific changes in fatty acid oxidation in hypoxic heart and skeletal muscle

Morash

Kotwica

Murray

2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Morash AJ, Kotwica AO, Murray AJ. Tissue-specific changes in fatty acid oxidation in hypoxic heart and skeletal muscle. Am J Physiol Regul Integr Comp Physiol 305: R534 -R541, 2013. First published June 19, 2013 doi:10.1152/ajpregu.00510.2012.-Exposure to hypobaric hypoxia is sufficient to decrease cardiac PCr/ATP and alters skeletal muscle energetics in humans. Cellular mechanisms underlying the different metabolic responses of these tissues and the time-dependent nature of these changes are currently unknown, but altered substrate utilization and mitochondrial function may be a contributory factor. We therefore sought to investigate the effects of acute (1 day) and more sustained (7 days) hypoxia (13% O 2) on the transcription factor peroxisome proliferator-activated receptor ␣ (PPAR␣) and its targets in mouse cardiac and skeletal muscle. In the heart, PPAR␣ expression was 40% higher than in normoxia after 1 and 7 days of hypoxia. Activities of carnitine palmitoyltransferase (CPT) I and ␤-hydroxyacyl-CoA dehydrogenase (HOAD) were 75% and 35% lower, respectively, after 1 day of hypoxia, returning to normoxic levels after 7 days. Oxidative phosphorylation respiration rates using palmitoyl-carnitine followed a similar pattern, while respiration using pyruvate decreased. In skeletal muscle, PPAR␣ expression and CPT I activity were 20% and 65% lower, respectively, after 1 day of hypoxia, remaining at this level after 7 days with no change in HOAD activity. Oxidative phosphorylation respiration rates using palmitoyl-carnitine were lower in skeletal muscle throughout hypoxia, while respiration using pyruvate remained unchanged. The rate of CO2 production from palmitate oxidation was significantly lower in both tissues throughout hypoxia. Thus cardiac muscle may remain reliant on fatty acids during sustained hypoxia, while skeletal muscle decreases fatty acid oxidation and maintains pyruvate oxidation. fatty acids; mitochondrial respiration; hypoxia; metabolism; heart HYPOBARIC HYPOXIA elicits a myriad of physiological responses that aim to increase oxygen availability at the tissues or decrease tissue oxygen demand (42). Central to this response is an acute increase in cardiac output, which in the face of atmospheric hypoxia can lead to an inability to match oxygen demand at the heart tissue itself (17). In a study of humans returning from exposure to hypobaric hypoxia at high altitude, resting energy levels were maintained in the subjects' skeletal muscle (9), whereas their hearts showed impaired energetics as indicated by decreased PCr/ATP (17). The cellular mechanisms underlying the different responses of these two tissues are unknown; however, the process of metabolic remodelling may differ under hypoxic conditions, and it has been suggested that altered substrate selection and mitochondrial respiration may be key factors in this regard (23,38,50).In the healthy heart, 90% of ATP production is generated via mitochondrial oxidative phosphorylation with 60 -70% of that energy being derived from lipid oxidation (3...

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“…Previous scientific expeditions have had, in general, a duration of 13-40 days. During these periods, the HA measures were repeated no more than three times, at the same altitude 2,14,18,19,22,36 or during the ascent. 27,40 Among works dealing with the issue of muscle fatigue, only two have explored the effects of acclimatization, and they reported conflicting results.…”

Section: Discussionmentioning

confidence: 99%

Myoelectric manifestations of fatigue during exposure to hypobaric hypoxia for 12 days

et al. 2004

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Lack of oxygen, as occurs at high altitude (HA), leads to a number of adaptive processes in muscle, but their precise nature is unclear. To better understand mechanisms of adaptations of the neuromuscular system to HA, we collected surface electromyographic (EMG) signals during a 12-day stay at 5,050 m above sea level (SL). The aim was to investigate the effect of hypobaric hypoxia on muscle-fiber membrane and motor-unit control properties. Surface EMG signals were recorded from the dominant biceps brachii muscle of six subjects at HA and 3 months after their return to SL. Supramaximal electrical stimuli (25 HZ) were delivered and voluntary isometric contractions at 40 and 80% of maximal voluntary torque were performed in 10 experimental sessions at HA and in 3 at SL. Maximal isometric torque was not altered at HA. Surface EMG spectral frequencies at the beginning of the voluntary contractions were greater at HA than SL. The rates of change of spectral frequencies and conduction velocity during the voluntary contractions were significantly larger at HA than SL. No differences in EMG variables were observed in the electrically elicited contractions. The maximal torque and surface EMG variables did not depend on the day of measure at HA. It was concluded that acute exposure to hypobaric hypoxia does not significantly affect the muscle-fiber membrane properties but does impact motor-unit control properties. This provides new insights in the understanding of motor control in extreme conditions of oxygen reduction, with relevance for sport and rehabilitation medicine, and may also explain the pathophysiological adaptations of the neuromuscular system occurring in such disorders as chronic obstructive pulmonary disease.

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Altitude acclimatization and energy metabolic adaptations in skeletal muscle during exercise

Cited by 85 publications

References 19 publications

HIF-1-driven skeletal muscle adaptations to chronic hypoxia: molecular insights into muscle physiology

HIF-1-driven skeletal muscle adaptations to chronic hypoxia: molecular insights into muscle physiology

Tissue-specific changes in fatty acid oxidation in hypoxic heart and skeletal muscle

Myoelectric manifestations of fatigue during exposure to hypobaric hypoxia for 12 days

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