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The role of mitophagy in the mechanism of genioglossal dysfunction caused by chronic intermittent hypoxia and the protective effect of adiponectin

  • Sleep Breathing Physiology and Disorders • Original Article
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Abstract

Purpose

Dysfunction of the genioglossus muscle is important in the pathogenesis of obstructive sleep apnea due to chronic intermittent hypoxia (CIH). Mitochondrial impairment resulting from hypoxia is mitigated by mitophagy to avoid cell apoptosis in cardiomyocytes. This project was designed to explore the effects of CIH on mitophagy in the genioglossus muscle and the impact of adiponectin (Ad).

Methods

One hundred eighty male SD rats were randomly divided into 3 groups (normal control [NC], CIH, and CIH + Ad groups), with 60 rats in each group observed for 5 weeks. Comparisons of serum Ad levels, mitochondrial structure and function, mitophagy, and cell apoptosis in the genioglossus were made at different time points.

Results

(1) The CIH group was significantly different from the NC group as follows: During the first 3 weeks, serum Ad levels, the reactive oxygen species (ROS), relative proteins and mRNA of mitophagy, autophagy biomarker LC3-II, and autophagosomes increased, while during the last 2 weeks, most parameters decreased. (2) There was no difference among the 3 groups in mitochondrial structure and function-associated mRNA during the first 3 weeks, while damaged mitochondrial structures were growing during the last 2 weeks. Exacerbation of apoptosis was also detected in the last 2 weeks. (3) All of the damage was partially alleviated in the CIH + Ad group in contrast to CIH group at the end of this study.

Conclusion

Disturbances of genioglossal mitophagy could be related to damaged mitochondrial structure and function induced by CIH, which could be alleviated by supplementation of exogenous Ad via increasing mitophagy.

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Acknowledgments

I would like to thank Dr. Clete Kushida, Mike Mutschelknaus, and ISRTP (International Sleep Research Training Program) for their expertise and help in writing the manuscript.

Funding

This research was supported by the National Natural Scientific Foundation of China (81600066, 81770086).

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Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Road, Nanjing, 210011, China

    Wenjing Wang, Yina Zhu & Ganzhu Feng

  2. Department of Respiratory Medicine, Zhongda Hospital Southeast University, 87 Dingjiaqiao, Nanjing, 210009, China

    Wenxiao Ding

  3. Department of Respiratory Medicine, Affiliated Hospital of Jiangsu University, 438 Jiangfang Road, Zhenjiang, 212001, China

    Hanpeng Huang

  4. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

    Ning Ding & Xilong Zhang

Authors
  1. Wenjing Wang
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  2. Wenxiao Ding
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  3. Hanpeng Huang
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  4. Yina Zhu
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  5. Ning Ding
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  6. Ganzhu Feng
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  7. Xilong Zhang
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Corresponding author

Correspondence to Xilong Zhang.

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This experiment was approved by the Animal Ethics Committee of Nanjing Medical University.

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The authors declare that they have no conflict of interest.

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Wang, W., Ding, W., Huang, H. et al. The role of mitophagy in the mechanism of genioglossal dysfunction caused by chronic intermittent hypoxia and the protective effect of adiponectin. Sleep Breath 25, 931–940 (2021). https://doi.org/10.1007/s11325-020-02211-0

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  • DOI: https://doi.org/10.1007/s11325-020-02211-0

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