非靶向和靶向脂质组学揭示2型糖尿病中动态脂质代谢变化

Untargeted and Targeted Lipidomics Unveil Dynamic Lipid Metabolism Alterations in Type 2 Diabetes.

作者信息

Feng Li, He Bingshu, Xia Jianzhen, Wang Zhonghua

机构信息

School of Agroforestry and Medicine, The Open University of China, Beijing 100039, China.

Center for Imaging and Systems Biology, College of Life and Environmental Sciences, Minzu University of China, Beijing 100081, China.

出版信息

Metabolites. 2024 Nov 10;14(11):610. doi: 10.3390/metabo14110610.

DOI:10.3390/metabo14110610

PMID:39590846

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11596168/

Abstract

BACKGROUND

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder with a growing body of evidence suggesting the central role of lipid metabolism in its pathogenesis. However, the dynamic changes in lipid metabolism across different stages of T2DM remain understudied.

OBJECTIVE

This study aimed to elucidate the temporal alterations in lipid metabolism in T2DM using an integrated lipidomics approach.

METHOD

Serum samples from 155 subjects were analyzed using LC-MS-based lipidomics, including untargeted and targeted approaches.

RESULTS

We identified significant alterations in 44 lipid metabolites in newly diagnosed T2DM patients and 29 in high-risk individuals, compared with healthy controls. Key metabolic pathways such as sphingomyelin, phosphatidylcholine, and sterol ester metabolism were disrupted, highlighting the involvement of insulin resistance and oxidative stress in T2DM progression. Moreover, 13 lipid metabolites exhibited diagnostic potential for T2DN, showing consistent trends of increase or decrease as the disease progressed.

CONCLUSION

Our findings underscore the importance of lipid metabolism in T2D development and identify potential lipid biomarkers for early diagnosis and monitoring of disease progression, which contribute to paving the way for novel therapeutic strategies.

摘要

背景

2型糖尿病（T2DM）是一种复杂的代谢紊乱疾病，越来越多的证据表明脂质代谢在其发病机制中起核心作用。然而，T2DM不同阶段脂质代谢的动态变化仍未得到充分研究。

目的

本研究旨在使用综合脂质组学方法阐明T2DM中脂质代谢的时间变化。

方法

使用基于液相色谱-质谱联用的脂质组学方法，包括非靶向和靶向方法，对155名受试者的血清样本进行分析。

结果

与健康对照相比，我们发现新诊断的T2DM患者中有44种脂质代谢物发生了显著变化，高危个体中有29种发生了显著变化。鞘磷脂、磷脂酰胆碱和甾醇酯代谢等关键代谢途径受到破坏，突出了胰岛素抵抗和氧化应激在T2DM进展中的作用。此外，13种脂质代谢物对T2DN具有诊断潜力，随着疾病进展呈现出一致的增加或减少趋势。