Metabolomics to identify fingerprints of carotid atherosclerosis in nonobese metabolic dysfunction-associated fatty liver disease

Journal of Translational Medicine

Research

Lishu Xu¹  Pingguang Lei²  Congxiang Shao³  Junzhao Ye³  Bihui Zhong³  Wei Wang⁴  Shiting Feng⁵ 

[1] Department of Gastroenterology and Hepatology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, and Guangdong Provincial Geriatrics Institute, No. 106 Zhongshan II Road, Yuexiu District, Guangzhou, China;Department of Gastroenterology, Shenzhen Baoan District Songgang People’s Hospital, No. 2, Shajiang Road, Songgang Street, Bao’an District, Shenzhen, China;Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, 510080, Guangzhou, China;Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, China;Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, China;

关键词: Cardiovascular disease;    Carotid atherosclerosis;    Metabolomics;    Metabolic dysfunction-associated fatty liver disease;    Nonobese;   

DOI  :  10.1186/s12967-022-03760-6

 received in 2022-08-30, accepted in 2022-11-06,  发布年份 2022

来源: Springer

【 摘 要 】

Background/aimsNonobese metabolic dysfunction-associated fatty liver disease (MAFLD) is paradoxically associated with improved metabolic and pathological features at diagnosis but similar cardiovascular diseases (CVD) prognosis to obese MAFLD. We aimed to utilize the metabolomics to identify the potential metabolite profiles accounting for this phenomenon.MethodsThis prospective multicenter cross-sectional study was conducted in China enrolling derivation and validation cohorts. Liquid chromatography coupled with mass spectrometry and gas chromatography-mass spectrometry were applied to perform a metabolomics measurement.ResultsThe study involved 120 MAFLD patients and 60 non-MAFLD controls in the derivation cohort. Controls were divided into two groups according to the presence of carotid atherosclerosis (CAS). The MAFLD group was further divided into nonobese MAFLD with/without CAS groups and obese MAFLD with/without CAS groups. Fifty-six metabolites were statistically significant for discriminating the six groups. Among the top 10 metabolites related to CAS in nonobese MAFLD, only phosphatidylethanolamine (PE 20:2/16:0), phosphatidylglycerol (PG 18:0/20:4) and de novo lipogenesis (16:0/18:2n-6) achieved significant areas under the ROC curve (AUCs, 0.67, p = 0.03; 0.79, p = 0.02; 0.63, p = 0.03, respectively). The combination of these three metabolites and liver stiffness achieved a significantly higher AUC (0.92, p < 0.01). In obese MAFLD patients, cystine was found to be significant with an AUC of 0.69 (p = 0.015), followed by sphingomyelin (SM 16:1/18:1) (0.71, p = 0.004) and de novo lipogenesis (16:0/18:2n-6) (0.73, p = 0.004). The combination of these three metabolites, liver fat content and age attained a significantly higher AUC of 0.91 (p < 0.001). The AUCs of these metabolites remained highly significant in the independent validation cohorts involving 200 MAFLD patients and 90 controls.ConclusionsDiagnostic models combining different metabolites according to BMI categories could raise the accuracy of identifying subclinical CAS.Trial registration The study protocol was approved by the local ethics committee and all the participants have provided written informed consent (Approval number: [2014] No. 112, registered at the Chinese Clinical Trial Registry, ChiCTR-ChiCTR2000034197)Graphical Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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