# The effects of graded hypoxia on gene expression related to oxygen sensing and metabolism

**Authors:** Josey Walker, Brent Ruby, Dustin Slivka

PMC · DOI: 10.1038/s41598-025-31608-8 · 2025-12-17

## TL;DR

This study found that recovering in hypoxic environments after exercise does not significantly change gene expression related to oxygen sensing and metabolism compared to normal oxygen levels.

## Contribution

The study identifies that graded hypoxia during recovery does not alter key gene expression levels related to oxygen sensing and metabolism in endurance athletes.

## Key findings

- Pulse oxygen saturation decreased with increasing simulated altitude during recovery.
- Gene expression of PGC-1α, HIF-1α, and HK increased after recovery, but no differences were found between hypoxia levels.
- No significant changes were observed in HIF-2α, PFK, FIS, MFN 2, and OPA gene expression across hypoxia levels.

## Abstract

To improve performance at altitude some endurance athletes undergo exposure to hypoxic stimulus during post exercise recovery, but this may impact gene expression related to exercise adaptation. The purpose of this study is to determine a hypoxic threshold and its impact on gene expression related to oxygen sensing, metabolism, and mitochondrial dynamics. Ten male participants (24 ± 4 years, 47.1 ± 9.5 ml·kg− 1·min− 1 ) completed 4 trials at least 7 days apart. Each trial consisted of cycling for one hour at 70% of Wpeak in normoxia before recovering for 6 h in a simulated environment [0 m, 1,667 m, 3,333 m, and 5,000 m]. Muscle samples were collected from the vastus lateralis before exercise and after recovery. Pulse oxygen saturation (SPO2) was measured before exercise, during exercise, and during recovery. SPO2 lowered with increasing elevation (p < 0.001 for all trials). Gene expression of PGC-1α, HIF-1α, and HK increased following recovery from exercise (p = 0.048, p = 0.013, and p = 0.014), but there were no differences between trials (p > 0.05). No differences were observed for HIF-2α, PFK, FIS, MFN 2, and OPA (p > 0.05). Post aerobic exercise recovery at graded levels of simulated hypoxia does not affect the expression of genes related to oxygen sensing, metabolism, and mitochondrial dynamics, compared to normoxia.

## Linked entities

- **Genes:** PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891], HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091], ATP12A (ATPase H+/K+ transporting non-gastric alpha2 subunit) [NCBI Gene 479], EPAS1 (endothelial PAS domain protein 1) [NCBI Gene 2034], Pfk (Phosphofructokinase) [NCBI Gene 36060], LINC01554 (long intergenic non-protein coding RNA 1554) [NCBI Gene 202299], MFN2 (mitofusin 2) [NCBI Gene 9927], opa (odd paired) [NCBI Gene 40605]

## Full-text entities

- **Genes:** MFN2 (mitofusin 2) [NCBI Gene 9927] {aka CMT2A, CMT2A2, CMT2A2A, CMT2A2B, CPRP1, HMSN6A}, PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891] {aka LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A}, EPAS1 (endothelial PAS domain protein 1) [NCBI Gene 2034] {aka ECYT4, HIF2A, HLF, MOP2, PASD2, bHLHe73}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, LINC01554 (long intergenic non-protein coding RNA 1554) [NCBI Gene 202299] {aka C5orf27, FIS}
- **Diseases:** hypoxic (MESH:D002534), hypoxia (MESH:D000860)
- **Chemicals:** oxygen (MESH:D010100)

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12804853/full.md

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Source: https://tomesphere.com/paper/PMC12804853