A Comprehensive Study on the Metabolic Characteristics and Molecular Mechanisms of Obstructive Sleep Apnea Syndrome Based on Metabolomics and Transcriptomics_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

GAN Kao ^1,2 , GAO Ming ^1,3 , WANG Weiye ¹ , WU Yuan ¹ ,  LI Jiqiang ^1,4 ,  CHEN Jiankun ^1,4

1. The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P. R. China;
2. The Emergency Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong 510006, P. R. China;
3. The Emergency Department, Nanhai District Hospital of Chinese Medicine (Guangdong Provincial Hospital of Integrated Chinese and Western Medicine), Guangdong 528000, P. R. China;
4. The Third General Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong 510006, P. R. China;

Corresponding?author：

LI Jiqiang, Email: lijiqiangjizhen@163.com; CHEN Jiankun, Email: chenjiankundoctor@126.com

Keywords：

Obstructive Sleep Apnea; Lipidomics; Transcriptomics; Glycerolipid Metabolism

DOI：

10.7507/1671-6205.202409001

Video：

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Objective The aim of this study was to investigate the changes in peripheral blood metabolites and transcriptomes in patients with obstructive sleep apnea (OSA) and to assess their diagnostic value as biomarkers. Methods In this study, we utilized liquid chromatography-tandem mass spectrometry (LC-MS/MS) lipid-targeted metabolomics to compare the metabolic profiles of 30 OSA patients with those of 30 healthy controls, identifying differential lipid metabolites. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we determined that the glycerolipid metabolism pathway was significantly different. Furthermore, we conducted transcriptome analysis on peripheral blood mononuclear cells (PBMCs) from six OSA patients and six healthy controls to evaluate the expression of molecules related to the pathway. Results A total of 168 differential lipid metabolites were identified, with significant differences in the glycerolipid metabolism pathway between OSA patients and healthy controls. Transcriptome analysis revealed that glycerolipid metabolism-related molecules GPAT, AGPAT, and LPIN were under expressed in OSA patient PBMCs, suggesting that the glycerolipid metabolism pathway is suppressed in OSA patients. Additionally, diagnostic value analysis showed that GPAT and AGPAT had high AUC values, indicating their potential as biomarkers for OSA. Conclusion The suppression of the glycerolipid metabolism pathway is closely related to the development of OSA, and the under expression of key genes in this pathway, such as GPAT, AGPAT, and LPIN, may be involved in the pathophysiological process of OSA. These findings not only provide a new perspective for understanding the pathogenesis of OSA but also offer new scientific evidence for the treatment of OSA from the perspective of glycerolipid metabolism regulation.

Citation： GAN Kao, GAO Ming, WANG Weiye, WU Yuan, LI Jiqiang, CHEN Jiankun. A Comprehensive Study on the Metabolic Characteristics and Molecular Mechanisms of Obstructive Sleep Apnea Syndrome Based on Metabolomics and Transcriptomics. Chinese Journal of Respiratory and Critical Care Medicine, 2025, 24(2): 97-106. doi: 10.7507/1671-6205.202409001 Copy

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2.	Maresky HS, Shpirer I, Klar MM, et al. Continuous positive airway pressure alters brain microstructure and perfusion patterns in patients with obstructive sleep apnea. Sleep Med, 2019, 57: 61-69.
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18.	黃艷陽, 隋國媛, 趙娜, 等. 茵陳蒿湯對代謝相關脂肪性肝病小鼠“腸TPH1-肝HTR2A軸”的影響. 世界科學技術-中醫藥現代化, 2023, 25(7): 2336-2343.
19.	羅云云, 張瀝元, 王心怡, 等. AGPAT2基因突變致先天性全身性脂肪營養不良伴發疹性黃瘤1例. 基礎醫學與臨床, 2023, 43(12): 1852-1856.
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21.	姜全奧, 鄧然, 夏仕林, 等. 脂滴代謝調控鐵死亡的研究進展. 藥學學報, 2024, 59(7): 1897-1904.

1. Basoglu OK, Midilli M, Midilli R, et al. Adherence to continuous positive airway pressure therapy in obstructive sleep apnea syndrome: effect of visual education. Sleep Breath, 2012, 16(4): 1193-1200.
2. Maresky HS, Shpirer I, Klar MM, et al. Continuous positive airway pressure alters brain microstructure and perfusion patterns in patients with obstructive sleep apnea. Sleep Med, 2019, 57: 61-69.
3. 彭程, 許紹蓉, 王彥, 等. 阻塞性睡眠呼吸暫停患者不同阻塞型呼吸事件的脈搏血氧飽和度曲線變化特點. 中國呼吸與危重監護雜志, 2023, 22(8): 539-545.
4. Senaratna CV, Perret JL, Lodge CJ, et al. Prevalence of obstructive sleep apnea in the general population: A systematic review. Sleep Med Rev, 2017, 34: 70-81.
5. Alterki A, Joseph S, Thanaraj TA, et al. Targeted Metabolomics Analysis on Obstructive Sleep Apnea Patients after Multilevel Sleep Surgery. Metabolites, 2020, 10(9): 358-373.
6. Olafiranye O, Adedayo AM. Obstructive sleep apnea and dyslipidemia: pathophysiological mechanisms. Sleep Breath, 2013, 17(2): 445-463.
7. 洪雪玲, 李永霞, 艾麗, 等. 阻塞性睡眠呼吸暫停合并2型糖尿病的機制. 中國呼吸與危重監護雜志, 2024, 23(9): 666-672.
8. Drager LF, Lopes HF, Maki-Nunes C, et al. The impact of obstructive sleep apnea on metabolic and inflammatory markers in consecutive patients with metabolic syndrome. PLoS One, 2010, 5(8): e12065.
9. Savransky V, Jun J, Li J, et al. Dyslipidemia and atherosclerosis induced by chronic intermittent hypoxia are attenuated by deficiency of stearoyl coenzyme A desaturase. Circ Res, 2008, 103(10): 1173-1180.
10. Veasey SC, Rosen IM. Obstructive Sleep Apnea in Adults. N Engl J Med, 2019, 380(15): 1442-1449.
11. Yang X, Niu X, Xiao Y, et al. MiRNA expression profiles in healthy OSAHS and OSAHS with arterial hypertension: potential diagnostic and early warning markers. Respir Res, 2018, 19(1): 194-211.
12. 中國醫師協會睡眠醫學專業委員會. 成人阻塞性睡眠呼吸暫停多學科診療指南. 中華醫學雜志, 2018, 98(24): 1902-1914.
13. 殷善開, 包玉倩, 關建, 等. 阻塞性睡眠呼吸暫停合并代謝綜合征診療專家共識(2022). 中華耳鼻咽喉頭頸外科雜志, 2023, 58(2): 99-110.
14. 王海鵬. 慢性間歇性低氧大鼠肝臟脂質代謝異常的機制和N-acetylcysteine的治療作用 [D]; 山東大學, 2018.
15. 李宏. 缺氧對脂肪細胞代謝及內分泌功能的影響 [D]; 石河子大學, 2012.
16. 關鵬. 慢性間歇性低氧引起大鼠心臟損傷的機制及白藜蘆醇的干預研究 [D]; 河北中醫學院, 2022.
17. Allaband C, Lingaraju A, Martino C, et al. Intermittent Hypoxia and Hypercapnia Alter Diurnal Rhythms of Luminal Gut Microbiome and Metabolome. mSystems, 2021, 6(3): e0011621.
18. 黃艷陽, 隋國媛, 趙娜, 等. 茵陳蒿湯對代謝相關脂肪性肝病小鼠“腸TPH1-肝HTR2A軸”的影響. 世界科學技術-中醫藥現代化, 2023, 25(7): 2336-2343.
19. 羅云云, 張瀝元, 王心怡, 等. AGPAT2基因突變致先天性全身性脂肪營養不良伴發疹性黃瘤1例. 基礎醫學與臨床, 2023, 43(12): 1852-1856.
20. Dai W, Zheng P, Luo D, et al. LPIN1 is a Regulatory Factor Associated With Immune Response and Inflammation in Sepsis. Front Immunol, 2022, 13: 820164.
21. 姜全奧, 鄧然, 夏仕林, 等. 脂滴代謝調控鐵死亡的研究進展. 藥學學報, 2024, 59(7): 1897-1904.

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A Comprehensive Study on the Metabolic Characteristics and Molecular Mechanisms of Obstructive Sleep Apnea Syndrome Based on Metabolomics and Transcriptomics

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