Skip to main content
Log in

Relationship between the mitochondria-derived peptide MOTS-c and insulin resistance in obstructive sleep apnea

  • Sleep Breathing Physiology and Disorders • Original Article
  • Published:
Sleep and Breathing Aims and scope Submit manuscript

Abstract

Purpose

The co-occurrence of obstructive sleep apnea (OSA) and obesity are common. Mitochondrial open reading frame of the 12S rRNA-c (MOTS-C) is one of the newly identified mitochondrial derivative peptides that play a role in the regulation of metabolic homeostasis. We aimed to examine the serum levels of MOTS-C to help understand the role of the disease in the pathophysiology, thereby investigating whether it can contribute to the appropriate treatment.

Materials and methods

Seventy patients with OSAS and 20 healthy controls were included. The serum MOTS-C level was measured in all patients. For each participant, demographic features, lipid profile, serum glucose levels, and insulin levels were also evaluated. Homeostatic model assessment indicator of insulin resistance (HOMA-IR) was calculated for all participants.

Results

Patients with OSAS (n = 70) were grouped as mild (n = 19), moderate (n = 19), and severe (n = 32). Patients with AHI ≤ 5 were considered as the healthy control group (n = 20). Mean age was 50.3 years and 74% (67/90) of the study sample was male. As expected, as the severity of OSA increased, BMI, insulin levels and HOMA-IR increased. MOTS-C levels were significantly lower in patients with OSA compared to healthy controls (p < 0.000) and we found that MOTS-C levels decreased as OSA severity increased. There was a negative correlation between serum MOTS-C levels and AHI and BMI (r = − 0.492, p < 0.001, r = − 0.382, p < 0.001, respectively). Serum MOTS-C levels were independently associated with AHI in BMI and HOMA-IR in linear regression analysis (p < 0.010, p < 0.007, p < 0.007, respectively).

Conclusion

Serum MOTS-C level is related to OSA and BMI. MOTS-C may be a useful new marker for early metabolic disorders in patients with OSA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. The report of an American Academy of Sleep Medicine Task Force (1999) Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep. 22:667–689

    Article  Google Scholar 

  2. Shechter A (2017) Obstructive sleep apnea and energy balance regulation: a systematic review. Sleep Med Rev 34:59–69. https://doi.org/10.1016/j.smrv.2016.07.001

    Article  PubMed  Google Scholar 

  3. Arnaud C, Bochaton T, Pépin JL, Belaidi E (2020) Obstructive sleep apnoea and cardiovascular consequences: pathophysiological mechanisms. Arch Cardiovasc Dis 113:350–358. https://doi.org/10.1016/j.acvd.2020.01.003

    Article  PubMed  Google Scholar 

  4. Li M, Li X, Yan L (2018) Obstructive sleep apnea syndrome and metabolic diseases. Endocrinology. 159:2670–2675

    Article  CAS  Google Scholar 

  5. Perantoni E, Filos D, Archontogeorgis K, Steiropoulos P, Chouvarda IC (2019) Pre-diabetic patients with severe obstructive sleep apnea: novel parameters of hypoxia during sleep correlate with insulin resistance. Annu Int Conf IEEE Eng Med Biol Soc 2019:5002–5005. https://doi.org/10.1109/EMBC.2019.8857457

    Article  CAS  PubMed  Google Scholar 

  6. Kanbay A, Kaya E, Buyukoglan H et al (2015) Correlation between pentraxin-3 and endothelial dysfunction in obstructive sleep apnea syndrome. Ann Thorac Med 10:199–203

    Article  CAS  Google Scholar 

  7. Drager LF, Jun JC, Polotsky VY (2010) Metabolic consequences of intermittent hypoxia: relevance to obstructive sleep apnea. Best Pract Res Clin Endocrinol Metab 24:843–851

    Article  CAS  Google Scholar 

  8. Singer K, Eng DS, Lumeng CN, Gebremariam A, M. Lee J (2014) The relationship between body fat mass percentiles and inflammation in children. Obesity. 22:1332–1336

    Article  CAS  Google Scholar 

  9. Gozal D (2009) Sleep, sleep disorders and inflammation in children. Sleep Med 10:12–16

    Article  Google Scholar 

  10. Matulewicz N, Karczewska-Kupczewska M (2016) Insulin resistance and chronic inflammation. Postepy Hig Med Dosw (Online) 70:1245–1258

    Google Scholar 

  11. Kanbay A, Ceylan E, Koseoglu İH et al (2018) Endocan: a novel predictor of endothelial dysfunction in obstructive sleep apnea syndrome. Clin Respir J 12:84–90

    Article  CAS  Google Scholar 

  12. Morino K, Petersen KF, Shulman GI (2006) Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction. Diabetes. 55:9–15

    Article  Google Scholar 

  13. Zamora-Mendoza R, Rosas-Vargas H, Ramos-Cervantes MT, Garcia-Zuniga P, Perez-Lorenzana H, Mendoza-Lorenzo P, Perez-Ortiz AC, Estrada-Mena FJ, Miliar-Garcia A, Lara-Padilla E, Ceballos G, Rodriguez A, Villarreal F, Ramirez-Sanchez I (2018) Dysregulation of mitochondrial function and biogenesis modulators in adipose tissue of obese children. Int J Obes 42:618–624. https://doi.org/10.1038/ijo.2017.274

    Article  CAS  Google Scholar 

  14. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P (2015) The mitochondrial-derived peptide MOTS-C promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab 21:443–454

    Article  CAS  Google Scholar 

  15. Zarse K, Ristow M (2015) A mitochondrially encoded hormone ameliorates obesity and insulin resistance. Cell Metab 21:355–356

    Article  CAS  Google Scholar 

  16. Du C, Zhang C, Wu W et al (2018) Circulating MOTS- C levels are decreased in obese male children and adolescents and associated with insulin resistance. Pediatr Diabetes 19:1058–1064. https://doi.org/10.1111/pedi.12685

    Article  CAS  Google Scholar 

  17. Qin Q, Delrio S, Wan J, Jay Widmer R, Cohen P, Lerman LO, Lerman A (2018) Downregulation of circulating MOTS-C levels in patients with coronary endothelial dysfunction. Int J Cardiol 254:23–27. https://doi.org/10.1016/j.ijcard.2017.12.001

    Article  PubMed  Google Scholar 

  18. Li H, Ren K, Jiang T, Zhao GJ (2018) MOTS-C attenuates endothelial dysfunction via suppressing the MAPK/NF-κB pathway. Int J Cardiol 268:40. https://doi.org/10.1016/j.ijcard.2018.03.031

    Article  PubMed  Google Scholar 

  19. Bonnet M, Carley D, Carskadon M et al (1992) EEG arousals: scoring rules and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association. Sleep 15:173–184

  20. Johns MW (1991) A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 14:540–545

    Article  CAS  Google Scholar 

  21. Shokolenko IN, Alexeyev MF (2015) Mitochondrial DNA: a disposable genome? Biochim Biophys Acta 1852:1805–1809

    Article  CAS  Google Scholar 

  22. Cataldo LR, Fernández-Verdejo R, Santos JL, Galgani JE (2018) Plasma MOTS-C levels are associated with insülin sensitivity in lean but not in obese individuals. Investig Med 66:1019–1022

    Article  Google Scholar 

  23. Ramanjaneya M, Bettahi I, Jerobin J et al (2019) Mitochondrial-derived peptides are down regulated in diabetes subjects. Front Endocrinol (Lausanne) 10:331

    Article  Google Scholar 

  24. Xanthopoulos MS, Berkowitz R, Tapia IE (2018) Effects of obesity therapies on sleep disorders. Metabolism. 84:109–117

    Article  CAS  Google Scholar 

  25. Bruyneel M, Kleynen P, Poppe K (2019) Prevalence of undiagnosed glucose intolerance and type 2 diabetes in patients with moderate-to-severe obstructive sleep apnea syndrome. Sleep Breath 24:1389–1395. https://doi.org/10.1007/s11325-019-01989-y

    Article  PubMed  Google Scholar 

  26. Hopps E, Caimi G (2015) Obstructive sleep apnea syndrome: links between pathophysiology and cardiovascular complications. Clin Invest Med 38:362–370

    Article  Google Scholar 

  27. Wang J, Yu W, Gao M, Zhang F, Gu C, Yu Y, Wei Y (2015) Impact of obstructive sleep apnea syndrome on endothelial function, arterial stiffening, and serum inflammatory markers: an updated meta-analysis and metaregression of 18 studies. J Am Heart Assoc 4. https://doi.org/10.1161/JAHA.115.002454

  28. Labarca G, Gower J, Lamperti L, Dreyse J, Jorquera J (2019) Chronic intermittent hypoxia in obstructive sleep apnea: a narrative review from pathophysiological pathways to a precision clinical approach. Sleep Breath 24:751–760. https://doi.org/10.1007/s11325-019-01967-4

    Article  PubMed  Google Scholar 

  29. Ozkok A, Ozkok S, Takır M, Yakar Hİ, Kanbay A (2018) Serum heparanase levels are associated with endothelial dysfunction in patients with obstructive sleep apnea. Clin Respir J 12:1693–1699

    Article  CAS  Google Scholar 

  30. Qin QD, Delrio S, Wan J et al (2018) Downregulation of circulating MOTS-C levels in patients with coronary endothelial dysfunction. Int J Cardiol 254:23–27

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Filiz Alkan Baylan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baylan, F.A., Yarar, E. Relationship between the mitochondria-derived peptide MOTS-c and insulin resistance in obstructive sleep apnea. Sleep Breath 25, 861–866 (2021). https://doi.org/10.1007/s11325-020-02273-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11325-020-02273-0

Keywords

Navigation