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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16.	关鹏. 慢性间歇性低氧引起大鼠心脏损伤的机制及白藜芦醇的干预研究 [D]; 河北中医学院, 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.	黄艳阳, 隋国媛, 赵娜, 等. 茵陈蒿汤对代谢相关脂肪性肝病小鼠“肠TPH1-肝HTR2A轴”的影响. 世界科学技术-中医药现代化, 2023, 25(7): 2336-2343.
19.	罗云云, 张沥元, 王心怡, 等. AGPAT2基因突变致先天性全身性脂肪营养不良伴发疹性黄瘤1例. 基础医学与临床, 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.	姜全奥, 邓然, 夏仕林, 等. 脂滴代谢调控铁死亡的研究进展. 药学学报, 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, 许绍蓉, 王彦, 等. 阻塞性睡眠呼吸暂停患者不同阻塞型呼吸事件的脉搏血氧饱和度曲线变化特点. 中国呼吸与危重监护杂志, 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, 艾丽, 等. 阻塞性睡眠呼吸暂停合并2型糖尿病的机制. 中国呼吸与危重监护杂志, 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. 中国医师协会睡眠医学专业委员会. 成人阻塞性睡眠呼吸暂停多学科诊疗指南. 中华医学杂志, 2018, 98(24): 1902-1914.
13. 殷善开, 包玉倩, 关建, 等. 阻塞性睡眠呼吸暂停合并代谢综合征诊疗专家共识(2022). 中华耳鼻咽喉头颈外科杂志, 2023, 58(2): 99-110.
14. 王海鹏. 慢性间歇性低氧大鼠肝脏脂质代谢异常的机制和N-acetylcysteine的治疗作用 [D]; 山东大学, 2018.
15. 李宏. 缺氧对脂肪细胞代谢及内分泌功能的影响 [D]; 石河子大学, 2012.
16. 关鹏. 慢性间歇性低氧引起大鼠心脏损伤的机制及白藜芦醇的干预研究 [D]; 河北中医学院, 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. 黄艳阳, 隋国媛, 赵娜, 等. 茵陈蒿汤对代谢相关脂肪性肝病小鼠“肠TPH1-肝HTR2A轴”的影响. 世界科学技术-中医药现代化, 2023, 25(7): 2336-2343.
19. 罗云云, 张沥元, 王心怡, 等. AGPAT2基因突变致先天性全身性脂肪营养不良伴发疹性黄瘤1例. 基础医学与临床, 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. 姜全奥, 邓然, 夏仕林, 等. 脂滴代谢调控铁死亡的研究进展. 药学学报, 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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