基于 LC-MS 的非靶向代谢组学研究发现,居住在郊区的老年人的代谢特征与肌肉减少症风险相关。

Metabolic signatures and risk of sarcopenia in suburb-dwelling older individuals by LC-MS-based untargeted metabonomics.

机构信息

Department of Rehabilitation Medicine, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China.

College of Rehabilitation Sciences, Shanghai University of Medicine and Health Sciences, Shanghai, China.

出版信息

Front Endocrinol (Lausanne). 2024 Jun 19;15:1308841. doi: 10.3389/fendo.2024.1308841. eCollection 2024.

Abstract

BACKGROUND

Untargeted metabonomics has provided new insight into the pathogenesis of sarcopenia. In this study, we explored plasma metabolic signatures linked to a heightened risk of sarcopenia in a cohort study by LC-MS-based untargeted metabonomics.

METHODS

In this nested case-control study from the Adult Physical Fitness and Health Cohort Study (APFHCS), we collected blood plasma samples from 30 new-onset sarcopenia subjects (mean age 73.2 ± 5.6 years) and 30 healthy controls (mean age 74.2 ± 4.6 years) matched by age, sex, BMI, lifestyle, and comorbidities. An untargeted metabolomics methodology was employed to discern the metabolomic profile alterations present in individuals exhibiting newly diagnosed sarcopenia.

RESULTS

In comparing individuals with new-onset sarcopenia to normal controls, a comprehensive analysis using liquid chromatography-mass spectrometry (LC-MS) identified a total of 62 metabolites, predominantly comprising lipids, lipid-like molecules, organic acids, and derivatives. Receiver operating characteristic (ROC) curve analysis indicated that the three metabolites hypoxanthine (AUC=0.819, 95% CI=0.711-0.927), L-2-amino-3-oxobutanoic acid (AUC=0.733, 95% CI=0.598-0.868) and PC(14:0/20:2(11Z,14Z)) (AUC= 0.717, 95% CI=0.587-0.846) had the highest areas under the curve. Then, these significant metabolites were observed to be notably enriched in four distinct metabolic pathways, namely, "purine metabolism"; "parathyroid hormone synthesis, secretion and action"; "choline metabolism in cancer"; and "tuberculosis".

CONCLUSION

The current investigation elucidates the metabolic perturbations observed in individuals diagnosed with sarcopenia. The identified metabolites hold promise as potential biomarkers, offering avenues for exploring the underlying pathological mechanisms associated with sarcopenia.

摘要

背景

非靶向代谢组学为肌少症的发病机制提供了新的见解。在这项基于 LC-MS 的非靶向代谢组学的巢式病例对照研究中,我们探索了与肌少症风险升高相关的血浆代谢特征。

方法

在成人体能与健康队列研究(APFHCS)的这项嵌套病例对照研究中,我们收集了 30 名新发肌少症患者(平均年龄 73.2±5.6 岁)和 30 名健康对照者(平均年龄 74.2±4.6 岁)的血浆样本,这些对照者按年龄、性别、BMI、生活方式和合并症进行匹配。采用非靶向代谢组学方法来辨别新诊断为肌少症患者的代谢组学特征改变。

结果

与正常对照组相比,使用液相色谱-质谱(LC-MS)进行全面分析共鉴定出 62 种代谢物,主要包括脂质、类脂分子、有机酸及其衍生物。受试者工作特征(ROC)曲线分析表明,黄嘌呤(AUC=0.819,95%CI=0.711-0.927)、L-2-氨基-3-氧代丁酸(AUC=0.733,95%CI=0.598-0.868)和 PC(14:0/20:2(11Z,14Z))(AUC=0.717,95%CI=0.587-0.846)这三种代谢物的曲线下面积最高。然后,观察到这些显著的代谢物在四个不同的代谢途径中明显富集,即“嘌呤代谢”、“甲状旁腺激素合成、分泌和作用”、“癌症中的胆碱代谢”和“结核病”。

结论

本研究阐明了诊断为肌少症患者的代谢紊乱。所鉴定的代谢物有望成为潜在的生物标志物,为探索与肌少症相关的潜在病理机制提供了途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3f/11220188/6d00a028bc40/fendo-15-1308841-g001.jpg

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