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Normalization of Oxygen Levels Induces a Metabolic Reprogramming in Livers Exposed to Intermittent Hypoxia Mimicking
Miguel Á Hernández-García1, Beatriz Aldave-Orzáiz2, Carlos Ernesto Fernández-García1
1Research Unit, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa, 28006 Madrid, Spain.
Antioxidants (Basel, Switzerland)
|August 28, 2025
Summary
Obstructive sleep apnea (OSA) treatment with CPAP improves liver health by normalizing oxygen levels. This reduces fatty liver disease (MASLD) and improves metabolic dysfunction by restoring fatty acid oxidation.
Area of Science:
- Hepatology
- Sleep Medicine
- Metabolic Disorders
Background:
- Obstructive sleep apnea (OSA) is linked to metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD).
- Intermittent hypoxia (IH) in OSA worsens MASLD via oxidative stress, inflammation, and lipid accumulation.
Purpose of the Study:
- To investigate how normalizing oxygen levels impacts metabolic dysfunction in OSA patients and mice.
- To assess the effects of continuous positive airway pressure (CPAP) therapy on MASLD in OSA patients.
Main Methods:
- Clinical study: 76 participants (44 OSA, 32 controls) analyzed for metabolic and liver markers before and after 18 months of CPAP.
- Experimental study: Mice exposed to IH followed by reoxygenation to assess liver changes and gene expression.
Main Results:
- OSA patients exhibited higher insulin resistance, triglycerides, VLDL, liver enzymes, and steatosis. CPAP therapy significantly improved these markers and liver steatosis scores.
- IH in mice caused liver lipid accumulation, oxidative stress, and inflammation; reoxygenation reversed these effects.
- IH impaired fatty acid oxidation (FAO) gene expression; reoxygenation restored FAO activity, enhancing lipid clearance despite lipogenesis.
Conclusions:
- CPAP therapy improves lipid profiles, liver function, and MASLD in OSA patients.
- Oxygen normalization, by restoring the FAO pathway, offers therapeutic potential for reversing IH-induced liver damage and metabolic reprogramming.
Keywords:
CPAPMASLDintermittent hypoxialipid metabolismliver steatosisobstructive sleep apneasteatosisMore Related Videos
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