Serum levels of the mitochondrial peptide MOTS-c were inversely related to obstructive sleep apnea severity, with OSA independently affecting MOTS-c levels even after accounting for BMI differences.
Independent of BMISleep apnea severity independently predicted lower MOTS-c levels even after accounting for body weight, suggesting a direct biological mechanism beyond obesity.
What the researchers found
Among 77 participants (53 OSA patients, 24 controls), serum MOTS-c levels were significantly correlated with BMI, AHI (Apnea-Hypopnea Index), and ODI (Oxygen Desaturation Index) independent of age. MOTS-c levels decreased progressively with OSA severity: patients with severe OSA had lower levels than those with moderate OSA, who had lower levels than those with mild OSA.
Critically, ANCOVA analysis with BMI as a covariate demonstrated that OSA severity was an independent factor influencing serum MOTS-c levels — meaning the relationship isn't simply explained by obesity. This suggests a direct biological connection between the intermittent oxygen deprivation in OSA and mitochondrial peptide production.
Why it matters
Sleep apnea affects an estimated 1 billion people worldwide and is linked to metabolic problems, cardiovascular disease, and diabetes. Understanding why metabolic dysfunction occurs in OSA could lead to new treatments. MOTS-c, as an exercise-mimicking mitochondrial peptide, could represent both a biomarker for OSA severity and a potential therapeutic target — supplementing MOTS-c might help counteract the metabolic damage caused by repeated oxygen drops during sleep.
How the study worked
This cross-sectional study enrolled 77 participants: 8 with mild OSA, 16 with moderate OSA, 29 with severe OSA, and 24 controls. Serum MOTS-c levels were measured by immunoassay. All participants underwent polysomnography (sleep study) and had complete blood counts, demographic data, and sleep questionnaires collected. Statistical analysis included correlation, ANOVA, and ANCOVA with BMI as covariate.
What this study cannot tell us
This is a cross-sectional observational study that cannot establish causation — it's unclear whether low MOTS-c causes OSA-related metabolic problems or is a consequence of them. The sample size of 77 is relatively small, particularly for subgroup analysis by OSA severity. MOTS-c measurement was from a single time point and may not reflect dynamic changes. The study did not assess whether CPAP treatment restores MOTS-c levels. Potential confounders like physical activity level and diet were not controlled.
How to read the evidence
This is a cross-sectional observational study with a modest sample size of 77 participants. While the statistical analysis properly controls for BMI, the study can only demonstrate association, not causation. Larger longitudinal studies would be needed to establish the clinical significance of this finding.
When this study was published
Published in 2025, this is very recent research connecting MOTS-c — a peptide only discovered in 2015 — to sleep medicine, representing an expanding frontier of mitochondrial peptide research.
The bigger picture
MOTS-c is part of an emerging class of mitochondria-derived peptides (MDPs) that are rewriting our understanding of mitochondria — not just as cellular power plants, but as signaling hubs that communicate with the rest of the body. This study connects MOTS-c to sleep medicine, adding to its known associations with exercise physiology, aging, and metabolic disease. If MOTS-c supplementation proves beneficial, it could address the metabolic complications of OSA without requiring weight loss or continuous positive airway pressure (CPAP).
Questions still open
- Does CPAP treatment for sleep apnea restore MOTS-c levels to normal?
- Could MOTS-c supplementation improve metabolic outcomes in sleep apnea patients?
- Is the reduction in MOTS-c caused by intermittent hypoxia (oxygen drops) during sleep, and if so, through what mechanism?
Common questions
What is MOTS-c and why does it matter for sleep apnea?
Could boosting MOTS-c levels help treat sleep apnea complications?
Read the original research
Reduced serum levels of mitochondria-derived peptide MOTS-c in patients with obstructive sleep apnea.
Sleep and biological rhythms, 23(3), 305-311
Citation
Luo, Zhuoding; Ji, Rui; Ye, Renjing; Shi, Yawen; Pang, Qingfeng; Yin, Min. (2025). Reduced serum levels of mitochondria-derived peptide MOTS-c in patients with obstructive sleep apnea.. Sleep and biological rhythms, 23(3), 305-311. https://doi.org/10.1007/s41105-025-00578-9