bims-oxygme Biomed News
on Oxygen metabolism
Issue of 2025–07–13
ten papers selected by
Onurkan Karabulut, Berkeley City College
  1. The effects of two days of intermittent exogenous ketosis at high altitude on baroreflex sensitivity and ventilation under hypoxic and hypercapnic conditions.
  2. Modulation of NAD metabolism by oxygen availability.
  3. Hypoxic exercise enhances post-exercise hypotension compared to normoxic exercise.
  4. Hyperbaric Oxygen Therapy as a Therapeutic Option for Patients with Fibromyalgia.
  5. Absence of a glutamatergic channel arrest mechanisms in hypoxic naked mole-rat cortex.
  6. The HIF axes in cancer: angiogenesis, metabolism, and immune-modulation.
  7. Effects of long-term very high-altitude exposure on cardiopulmonary function of healthy adults in plain areas.
  8. Mitochondrial Ucp4 Ameliorates Motor Disorders by Protecting Cerebellar Purkinje Cells from Oxidative Stress in Intermittent Hypobaric Hypoxia Mice.
  9. Hypoxia: A Raptor mutant survives in thin air.
  10. High-Altitude Impacts on Gut Microbiota: Accelerated Aging and the Urgency for Targeted Health Interventions.
  1. Am J Physiol Regul Integr Comp Physiol. 2025 Jul 11.
    The effects of two days of intermittent exogenous ketosis at high altitude on baroreflex sensitivity and ventilation under hypoxic and hypercapnic conditions.
    Benjamin J Narang, Domen Tominec, Myrthe Stalmans, Grégoire P Millet, Chiel Poffé, Tadej Debevec.
      High-altitude (HA) exposure induces an integrated physiological response to mitigate hypoxemia. Exogenous ketosis at simulated HA was previously shown to accentuate sympathetic activation, and attenuate pulse oxygen saturation (SpO2) decreases through hyperventilation. The aim of this study was to extend these findings by investigating the effects of intermittent exogenous ketosis (IEK) across two days at terrestrial HA (3375 m) on baroreflex, heart rate variability, and hypoxic/hypercapnic ventilatory responses. 34 healthy active adults completed neutral, hypoxic, and hypercapnic (0.03 FiCO2) exposures, each comprising six minutes of seated rest, once at sea level (SL) and once after two days at HA. Across the two days, participants intermittently ingested either ketone monoester supplements (IEK) or placebo (PLA). During each exposure, blood pressure, ventilation, SpO2, and end-tidal CO2 pressure (PETCO2) were continuously recorded, and arterialized capillary blood gas content was measured in the final 30 s. Baroreflex sensitivity and time-domain metrics of heart rate variability were reduced at HA (p = 0.006-0.043), but unaffected by group (p = 0.288-0.525). However, ventilation at HA under all three conditions was significantly higher in IEK compared to PLA (all p < 0.001). In hypoxia, this induced a higher SpO2 (p = 0.038) and capillary O2 pressure (p = 0.003). In hypercapnia, this induced a lower PETCO2 and capillary CO2 tension (both p < 0.001). These results extend previous findings, suggesting that IEK enhances ventilation at terrestrial HA and after two days of exposure, with this effect being independent from baroreflex sensitivity or heart rate variability changes.
    Keywords:  Autonomic control; Blood pressure; Hypobaric hypoxia; Ketone bodies; Sympathetic nervous system
    DOI:  https://doi.org/10.1152/ajpregu.00125.2025
  2. Free Radic Biol Med. 2025 Jul 08. pii: S0891-5849(25)00818-4. [Epub ahead of print]
    Modulation of NAD metabolism by oxygen availability.
    Johannes Burtscher, Tobias Dünnwald, Giuseppe Paglia.
      Reduced oxygen availability (hypoxia) can result in decreased energy levels, perturbed redox homeostasis and permanent cellular damage. Efficient hypoxic stress responses and the induction of protective adaptations are crucial to prevent hypoxic damage and can be targeted to improve cellular resilience and health. Nicotinamide adenine dinucleotide (NAD) metabolism is highly sensitive to changes in oxygen availability and interacts with other stress pathways, such as the oxygen-regulated transcription factors hypoxia-inducible factors (HIFs), to orchestrate cellular responses and adaptations to hypoxia. We evaluate what is known about this interaction, how it may be modulated and which benefits could be expected from related therapeutic interventions. We further discuss, which future research is needed to develop therapeutic strategies targeting the hypoxic response-NAD axis.
    Keywords:  hypoxia inducible factor; metabolic reprogramming; mitochondrial functions; nicotinamide adenine dinucleotide; oxidative stress; oxygen; redox homeostasis
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.07.014
  3. Int J Sports Med. 2025 Jul 07.
    Hypoxic exercise enhances post-exercise hypotension compared to normoxic exercise.
    Tae-Jin Kim, Min-Hyeok Jang, Jean-Hee Han, Hyun-Chul Jung, Jung-Hyun Kim.
      This study aimed to investigate the effect of aerobic exercise under hypoxic conditions (FiO2: 14.9%) on post-exercise hypotension compared to normoxic exercise matched for mechanical and physiological intensities. Twenty sedentary men completed three exercise sessions using a crossover design: (1) hypoxic exercise at 50% of peak power output, (2) normoxic exercise at 50% of peak power output (normoxic exercise matched for mechanical intensity), and (3) normoxic exercise with heart rates matched for hypoxic exercise. Expired gases and peripheral and muscle oxygen saturation were measured during the exercise. Blood pressure and hemodynamic variables were assessed before and after each exercise session. Hypoxic exercise and normoxic exercise matched for physiological intensity elicited higher heart rate, oxygen consumption, and ventilation compared to normoxic exercise matched for mechanical intensity (p<0.05). Hypoxic exercise showed the lowest ventilation efficiency (p<0.01) and the most severe systemic and muscle hypoxemia (p<0.01) during exercise. Only hypoxic exercise induced significant post-exercise hypotension (-6.9 mmHg; p<0.01) with a significant increase in common femoral artery diameter during recovery (p<0.05). Our findings suggested that hypoxic exercise significantly enhances post-exercise vasodilation compared to normoxic exercise, resulting in greater post-exercise hypotension. This highlighted hypoxic exercise as a promising strategy for managing hypertension with reduced mechanical stress, particularly beneficial for individuals with low exercise tolerance.
    DOI:  https://doi.org/10.1055/a-2602-9020
  4. Curr Rheumatol Rev. 2025 Jul 07.
    Hyperbaric Oxygen Therapy as a Therapeutic Option for Patients with Fibromyalgia.
    Philippe Pencalet.
       INTRODUCTION/OBJECTIVE: This narrative review has briefly outlined the mechanisms of action underlying the therapeutic effects of hyperbaric oxygen (HBO). It was designed to provide researchers and healthcare professionals with a broad overview of the benefits and potential drawbacks of using HBO in FM patients.
    METHODS: For this review, we searched PubMed/Medline, Cochrane Library, Embase, and Google Scholar databases for articles published between 2000 and 2023, using the following search terms: "hyperbaric oxygen therapy", "fibromyalgia", and "physical exercise".
    RESULTS: In total, more than 90 publications were retrieved, 45 of which were analyzed in depth. The majority of the studies retrieved were of an observational design, whereas there were only a few randomized trials and very few reviews. Based on the compiled literature, there is further support for the hypothesis that reduced oxygen availability may be at the origin of the structural degeneration observed in the muscles of FM patients. In the absence of a universally accepted cure for FM, the therapeutic approach must be multidisciplinary and multimodal. It should be noted that many questions remain unanswered. What is the optimal dose-response range, duration of treatment, and associated economic cost? Larger controlled trials are needed to determine the exact role of HBO as an adjuvant therapy for FM patients.
    CONCLUSION: Based on the published literature, repeated exposure to HBO may be a promising therapeutic adjunct for FM patients. However, more clinical research is needed before HBO can be established as a reliable approach for FM patients.
    Keywords:  Hyperbaric oxygen therapy; aerobic.; chronic pain conditions; fibromyalgia; neuroplasticity
    DOI:  https://doi.org/10.2174/0115733971370773250625104646
  5. Neurosci Lett. 2025 Jul 04. pii: S0304-3940(25)00197-1. [Epub ahead of print]863 138309
    Absence of a glutamatergic channel arrest mechanisms in hypoxic naked mole-rat cortex.
    George Otell, Liam Eaton, Maria Roy, Matthew E Pamenter.
      In the brain of hypoxia-intolerant vertebrates, hypoxia induces neuronal depolarization, chronic activation of voltage-gated excitatory glutamatergic receptors, and rapid accumulation of Ca2+ in the cytosol, which induces downstream activation of cell death pathways. Conversely, deleterious Ca2+ accumulation and cell death is avoided in the brain of hypoxia-tolerant vertebrates. One neuroprotective adaptation that is present in some of the most hypoxia-tolerant vertebrates is channel arrest, whereby Ca2+ ion influx through glutamate receptors is reduced in hypoxia, and cytotoxic accumulation of Ca2+ is avoided. Naked mole-rats are a hypoxia-tolerant mammal and avoid neurotoxic Ca2+ accumulation during hypoxia; however, the underlying mechanisms are poorly understood. In the present study, we tested the hypothesis that channel arrest of glutamatergic receptors occurs in hypoxic naked mole-rat neurons, which would help to limit Ca2+ influx during hypoxia. Using the Ca2+-sensitive fluorophore Fura-2, we measured Ca2+ flux through glutamatergic receptors in live brain slices exposed to a normoxic or hypoxic (1 % O2) perfusate and following application of either glutamate or NMDA to stimulate glutamatergic receptors. We found no differences in the magnitude of the evoked Ca2+ transients or the total amount of Ca2+ movement following ligand stimulus. Our results indicate that channel arrest is not an important strategy to limit deleterious Ca2+ influx into naked mole-rat neurons during hypoxia. Other mechanisms, such as enhanced mitochondrial buffering of cytosolic Ca2+, may play a more important role in hypoxic Ca2+ homeostasis in this species.
    Keywords:  Excitotoxic cell death; Glutamate; Hypoxia; NMDA receptor
    DOI:  https://doi.org/10.1016/j.neulet.2025.138309
  6. Trends Biochem Sci. 2025 Jul 09. pii: S0968-0004(25)00135-5. [Epub ahead of print]
    The HIF axes in cancer: angiogenesis, metabolism, and immune-modulation.
    Karen Acuña-Pilarte, Mei Yee Koh.
      The hypoxia-inducible factors (HIFs) are central transcriptional mediators of the cellular response to hypoxia. HIF activation typically drives a physiologically beneficial adaptive response to hypoxia. However, within solid tumors, the HIF-driven adaptation to hypoxia results in alterations within major cancer cell signaling axes, including those regulating angiogenesis, metabolism, and immune modulation, which profoundly impact tumor progression. This review describes established and recent findings of the role of HIFs in the regulation of these major axes, and the impact of the 'HIF axes' on tumor progression and response to therapy. Current and emerging therapies targeting these axes will also be discussed.
    Keywords:  hypoxia; hypoxia-inducible factor (HIF); metabolic reprogramming; solid tumors; therapeutics targeting; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.tibs.2025.06.005
  7. Sci Rep. 2025 Jul 10. 15(1): 24826
    Effects of long-term very high-altitude exposure on cardiopulmonary function of healthy adults in plain areas.
    Chengshuo Wang, Linli Zhang, Zejian Liu, Ziyan Chen, Ying Li, Yanxin Fu, Aomeng Xiang, Jingman Qi, Ruoxuan Zhao, Liang Wu, Lei Gu.
      Due to the unique plateau climate, such as low atmospheric pressure, hypoxia, cold, and dryness, people in plain areas will have a series of physiological and pathological changes after entering the plateau. This observational study was designed to assess the effects of long-term very high-altitude (HA) exposure on the cardiopulmonary function of healthy adults in plain areas through cardiopulmonary exercise testing (CPET). We tracked and observed 45 healthy adult men or women from the plain area (Beijing, with an altitude of approximately 40 m). They worked and lived in very HA areas (Lhasa, with an altitude of approximately 3,700 m) for 5 months before returning to plain areas. Participants completed health checkups, including basic physiological indexes, static pulmonary function tests, and CPET at baseline and after very HA exposure. The resulting data showed that after long-term very HA exposure, multiple CPET indicators significantly decreased (p < 0.05), including peak oxygen uptake, anaerobic threshold, peak work rate, oxygen uptake/work rate, peak oxygen uptake/heart rate, oxygen uptake efficiency slope, peak minute ventilation, peak end-expiratory carbon dioxide partial pressure, and peak cardiac output. The minute ventilation/carbon dioxide production slope was significantly higher than that before very HA exposure (p = 0.004). There were no significant changes in static pulmonary function (p > 0.05). In conclusion, long-term very HA exposure can lead to varying degrees of negative effects on cardiopulmonary function (including respiratory, circulatory, and metabolic function decline) in healthy adults in plain areas. The abnormality of related functional indicators may indicate that the body's adaptive compensatory mechanism to the high altitude hypobaric hypoxia environment is decompensated. It is suggested that it is necessary to implement individualized cardiopulmonary rehabilitation training as soon as possible after long-term very HA exposure to mitigate functional decline in individuals.
    Keywords:  Cardiopulmonary endurance; Cardiopulmonary exercise testing; Cardiopulmonary function; High altitude
    DOI:  https://doi.org/10.1038/s41598-025-07474-9
  8. Antioxid Redox Signal. 2025 Jul 09.
    Mitochondrial Ucp4 Ameliorates Motor Disorders by Protecting Cerebellar Purkinje Cells from Oxidative Stress in Intermittent Hypobaric Hypoxia Mice.
    Fei-Fei Wu, Bo-Zhi Liu, Rui-Qing Wang, Yun-Qiang Huang, Hui Liu, Zi-Wei Ni, Bo-Yang Li, Yu-Ze Sun, Yan-Ling Yang, Ya-Yun Wang.
      Acute altitude hypoxia is a syndrome that manifests at elevations exceeding 2500 m, posing significant health challenges to individuals who travel or work at high altitudes. Uncoupling proteins are integral proteins located within the mitochondrial inner membrane, playing a crucial role in modulating proton leakage across the mitochondrial membrane. This study investigates the potential role of uncoupling protein 4 (Ucp4) overexpression in an intermittent hypobaric hypoxia (IHH) model and its underlying mechanisms in the cerebellar dyskinesia phenotype. An IHH model was developed using a low-pressure hypoxic chamber, exposing mice to 16 h of hypoxia daily for 5 days. Three mouse strains were used: C57BL/6J, Pcp2Cre; Ucp4fl/fl, and Pcp2Cre; Mito-GFP. Behavioral tests, including rotarod, open field, balance beam, and Morris water maze, were conducted. Ucp4-overexpressing virus was administered to cerebellar lobes 4/5. Mitochondrial morphology was assessed via transmission electron microscopy, 3D reconstruction, and network analysis, while function was evaluated through reactive oxygen species, mitochondrial membrane potential (MMP), glutathione/glutathione disulfide ratio, adenosine triphosphate levels, qPCR, and Western blotting. Results showed that IHH induces hypoactivity without affecting spatial cognition. IHH-induced hypoactivity is linked to Ucp4 upregulation and increased mitochondrial fragmentation in Purkinje cells (PCs), though overall mitochondrial dynamics remain balanced. Ucp4 deficiency exacerbates IHH-induced hypoactivity and mitochondrial fragmentation. Conversely, Ucp4 overexpression in PCs significantly alleviates these effects. Mechanistically, Ucp4 protects PCs by stabilizing MMP and regulating oxidative stress, maintaining mitochondrial integrity. This study reveals that Ucp4 protects cerebellar PCs from oxidative stress in IHH, improving motor function and identifying Ucp4 as a potential therapeutic target for intermittent high-altitude syndrome. Antioxid. Redox Signal. 00, 000-000.
    Keywords:  Intermittent hypobaric hypoxia; Purkinje cells; hypoactivity; membrane potential homeostasis; mitochondrial uncoupling proteins Ucp4; oxidative stress
    DOI:  https://doi.org/10.1089/ars.2024.0853
  9. Curr Biol. 2025 Jul 07. pii: S0960-9822(25)00657-8. [Epub ahead of print]35(13): R662-R664
    Hypoxia: A Raptor mutant survives in thin air.
    David J Reiner.
      A recent study in Caenorhabditis elegans has identified a temperature-sensitive mutation in the mTORC1 component Raptor that confers hypoxia resistance and is associated with reduced protein synthesis but not increased autophagy. These findings point to mTORC1 as a promising target in hypoxia-related conditions.
    DOI:  https://doi.org/10.1016/j.cub.2025.05.041
  10. High Alt Med Biol. 2025 Jul 07.
    High-Altitude Impacts on Gut Microbiota: Accelerated Aging and the Urgency for Targeted Health Interventions.
    Zhexin Ni, Yongqiang Zhou, Mingyang Chang, Tiantian Xia, Wei Zhou, Yue Gao.
      The human gut microbiota is integral to the aging process, and its composition is notably influenced by the unique environmental pressures of high-altitude plateaus, characterized by hypobaric and hypoxic conditions. This study explores the correlation between physiological aging and gut microbiota among high-altitude plateau inhabitants, an essential aspect of health preservation in such regions. We conducted a metagenomic analysis of fecal samples from 105 individuals who migrated to high-altitude areas before the age of 20. Our results demonstrate that advancing age and prolonged high-altitude living significantly modify the gut microbiota, evidenced by reduced diversity and an elevated Firmicutes to Bacteroidetes (F/B) ratio in older subjects. Notably, the abundance of the anti-aging bacterium Akkermansia muciniphila (A. muciniphila) inversely correlates with age, showing a significant decline post the age of 25. A comparative analysis of 2,007 individuals from lower altitudes revealed a similar negative correlation between A. muciniphila and age, with a decline evident from age 38. These findings indicate that the high-altitude plateau environment may accelerate the decline of A. muciniphila by 10 years, underscoring the need for targeted health strategies for high-altitude populations.
    Keywords:  Akkermansia muciniphila; aging; gut microbiota; high altitude
    DOI:  https://doi.org/10.1089/ham.2025.0016
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