ArticleGenome medicine2009
Metabolic adaptation of skeletal muscle to high altitude hypoxia: how new technologies could resolve the controversies.
Article in Genome medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- Effects of Dietary Nitrates on Time Trial Performance in Athletes with Different Training Status: Systematic Review.Nutrients · 2020Pooled it
- The effect of acute beetroot juice consumption prior to climbing on lower-body isokinetic and isometric strength, aerobic power, and muscle soreness among mountain climbers.Journal of the International Society of Sports Nutrition · 2025Trial
- Trial
- Metabolomic profiles are reflective of hypoxia-induced insulin resistance during exercise in healthy young adult males.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Trial
- Oral Coenzyme Q10 supplementation does not prevent cardiac alterations during a high altitude trek to everest base cAMP.High altitude medicine & biology · 2014Trial
- Human adaptation to high-altitude: A contemporary comparison of the oxygen cascade in Andean, Tibetan and Ethiopian highlanders.Experimental physiology · 2026Review
- Effects and adaptation of high-altitude hypoxia on lipid metabolism: mechanisms and health implications.Frontiers in physiology · 2026Review
- Characterization of metabolic changes and adaptive remodeling during a hypobaric hypoxic exploration atmosphere environment.Frontiers in physiology · 2026Article
- High-altitude mountaineering induces adaptive gut microbiome shifts associated with dietary intake and performance markers.Scientific reports · 2025Article
- Placental mitochondria in high-altitude pregnancy: metabolic adaptations and a toolkit for respiratory assessment.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- L-Arginine and Nitric Oxide in Vascular Regulation-Experimental Findings in the Context of Blood Donation.Nutrients · 2025Review
- Metabolic insights into hypoxia adaptation in adolescent athletes at different altitudes: a cross-sectional study.Frontiers in molecular biosciences · 2025Article
- Exploring the Impact of Resistance Training at Moderate Altitude on Metabolic Cytokines in Humans: Implications for Adipose Tissue Dynamics.International journal of molecular sciences · 2024Article
- PKM2 regulates metabolic flux and oxidative stress in the murine heart.Physiological reports · 2024Article
- Complex II ambiguities-FADHThe Journal of biological chemistry · 2024Review
- Effect of hypobaric hypoxia on the fiber type transition of skeletal muscle: a synergistic therapy of exercise preconditioning with a nanocurcumin formulation.Journal of physiology and biochemistry · 2023Article
- Chronic developmental hypoxia alters mitochondrial oxidative capacity and reactive oxygen species production in the fetal rat heart in a sex-dependent manner.Journal of pineal research · 2022Article
- Redox status biomarkers in the fast-twitch extensor digitorum longus resulting from the hypoxic exercise.Nagoya journal of medical science · 2022Article
- Targeting the Mild-Hypoxia Driving Force for Metabolic and Muscle Transcriptional Reprogramming of Gilthead Sea Bream (Biology · 2021Article
- High-altitude hypoxia induced reactive oxygen species generation, signaling, and mitigation approaches.International journal of biometeorology · 2021Review
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In most tissues of the body, cellular ATP production predominantly occurs via mitochondrial oxidative phosphorylation of reduced intermediates, which are in turn derived from substrates such as glucose and fatty acids. In order to maintain ATP homeostasis, and therefore cellular function, the mitochondria require a constant supply of fuels and oxygen. In many disease states, or in healthy individuals at altitude, tissue oxygen levels fall and the cell must meet this hypoxic challenge to maintain energetics and limit oxidative stress. In humans at altitude and patients with respiratory disease, loss of skeletal muscle mitochondrial density is a consistent finding. Recent studies that have used cultured cells and genetic mouse models have elucidated a number of elegant adaptations that allow cells with a diminished mitochondrial population to function effectively in hypoxia. This article reviews these findings alongside studies of hypoxic human skeletal muscle, putting them into the context of whole-body physiology and acclimatization to high-altitude hypoxia. A number of current controversies are highlighted, which may eventually be resolved by a systems physiology approach that considers the time-or tissue-dependent nature of some adaptive responses. Future studies using high-throughput metabolomic, transcriptomic, and proteomic technologies to investigate hypoxic skeletal muscle in humans and animal models could resolve many of these controversies, and a case is therefore made for the integration of resulting data into computational models that account for factors such as duration and extent of hypoxic exposure, subjects' backgrounds, and whether data have been acquired from active or sedentary individuals. An integrated and more quantitative understanding of the body's metabolic response to hypoxia and the conditions under which adaptive processes occur could reveal much about the ways that tissues function in the very many disease states where hypoxia is a critical factor.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.