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Bariatric Surgery

Effect of positive pressure ventilation and bariatric surgery on extracellular vesicle microRNAs in patients with severe obesity and obstructive sleep apnea

International Journal of Obesity volume 47, pages 24–32 (2023)Cite this article

Subjects

Abstract

Introduction

Obstructive sleep apnea (OSA) and severe obesity share a common pathophysiological phenomenon, systemic and tissue hypoxia. Hypoxaemia modifies microRNA expression, particularly, extracellular vesicles microRNAs which are involved in the progression of cardiovascular diseases, metabolic syndrome and cancer. We aim to evaluate extracellular vesicle miRNAs among patients with severe obesity with and without OSA and the effect of OSA and severe obesity treatment: continuous positive airway pressure (CPAP) and bariatric surgery.

Methods

Patients were selected from the Epigenetics Modification in Morbid Obesity and Obstructive Sleep Apnea (EPIMOOSA) study (NCT03995836), a prospective observational study of patients undergoing bariatric surgery. Patients were divided into OSA (Apnea-hyponea index (AHI) > 10) and non-OSA (AHI < 10). Patients with OSA were treated with CPAP for 6 months. Then, all patients had bariatric surgery and re-evaluated 12 months later. At each visit, blood samples were obtained for biobanking. Subsequently, extracellular vesicles were extracted, and then, miRNA expression was analysed.

Results

15 patients with OSA and 9 without OSA completed the protocol. At baseline, patients with OSA showed higher miR16, miR126 and miR320 (p < 0.05) and lower miR223 expression (p < 0.05) than those without OSA. In patients with severe obesity and OSA, after 6 months with CPAP, we observed a significant decrease in miR21 (p < 0.01), miR126 (p < 0.001) and miR320 (p < 0.001), with no changes in any miRNA in patients without OSA. No changes were detected in any miRNA after 6 months of bariatric surgery in patients with or without OSA.

Conclusion

Co-existance of OSA and severe obesity alters the profile of extracellular vesicle miRNAs. Bariatric surgery and weight loss did not reverse this effect meanwhile the treatment with CPAP in patients with severe obesity and OSA showed a recovery outcome in those extracellular vesicle miRNAs. Those facts remark the need for OSA screening in patients with severe obesity.

Clinical trial registration

The study has also been registered at ClinicalTrials.gov identifier: NCT03995836.

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Fig. 1: Hypothetical relationship between chronic tissue hypoxia due to obesity and chronic intermittent hypoxia due to obstructive sleep apnea [16].
Fig. 2: Flowchart.
Fig. 3: Circulating EV-miRNA relative expression differences in patients with severe obesity with/without obstructive sleep apnea.
Fig. 4: Evolution of circulating EV-miRNA relative expression. Positive airway pressure and bariatric surgery effect.

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Data availability

The data are avalaible upon request.

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Acknowledgements

To my colleagues in the pulmonology department at Royo Villanova Hospital.

Funding

This research project has received grants from the Instituto Carlos III, Madrid, Spain PI15/01940, PI18/01524, PI21/01954), the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR-2017), and the Aragon Society of the Respiratory System (SADAR-2016).

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Author notes

  1. These authors contributed equally: J. Lázaro, D. Sanz-Rubio.

Authors and Affiliations

  1. Respiratory Service, Hospital Royo Villanova, Zaragoza, Spain

    J. Lázaro, P. Clavería & A. Castanera

  2. Translational Research Unit, Hospital Universitario Miguel Servet, IIS Aragón, Zaragoza, Spain

    J. Lázaro, D. Sanz-Rubio & J. M. Marin

  3. CIBER Enfermedades Respiratorias, Madrid, Spain

    J. Lázaro, D. Sanz-Rubio & J. M. Marin

  4. Endocrinology and Nutrition Service, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain

    C. Cabrejas

  5. Bariatric Surgery Unit, Hospital Royo Villanova, Zaragoza, Spain

    J. Fernando

  6. Department of Medicine, University of Zaragoza, Zaragoza, Spain

    J. M. Marin

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Contributions

JL conceived, designed, wrote and approved the final version. DSR contributed to the design, writing, lab work and revised the paper. PC, CC, JF and AC contributed to acquire data. JMM contributed to the design, writing and revision of the paper.

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Correspondence to J. Lázaro.

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The authors declare no competing interests.

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The study has been approved by the Aragon Institute of Health Sciences (Ethics Committee for Clinical Research of Aragon number: 23/2014). In accordance with recommendations from the Declaration of Human Rights, the Helsinki Conference and the IACS, patients must sign the informed consent form before being enroled in the study.

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Lázaro, J., Sanz-Rubio, D., Clavería, P. et al. Effect of positive pressure ventilation and bariatric surgery on extracellular vesicle microRNAs in patients with severe obesity and obstructive sleep apnea. Int J Obes 47, 24–32 (2023). https://doi.org/10.1038/s41366-022-01230-z

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