Department of Global Health, School of Public Health, Wuhan University, Wuhan, China; Global Health Institute, School of Public Health, Wuhan University, Wuhan, China.
Climate, Air Quality Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
J Hazard Mater. 2024 May 5;469:133864. doi: 10.1016/j.jhazmat.2024.133864. Epub 2024 Feb 22.
Insulin resistance (IR), linked to air pollution, is an initial stage of early-onset Type 2 diabetes mellitus (T2DM). While ceramide metabolism plays an important role in IR pathogenesis, the effects of air pollution on this process and its mechanisms remain unclear. We recruited young adults aged 18-30 years to a panel study in Wuhan, China. Using personal portable devices and stationary monitoring stations, we tracked particulate matter with aerodynamic diameters≤ 2.5 µm (PM) and Ozone (O) levels. Liquid chromatography/mass spectrometry (LC-MS) based metabolomics quantified ceramide metabolism, and Illumina Infinium Human Methylation 850 kBeadChip assay measured deoxyribonucleic acid (DNA) methylation. Linear mixed-effects models assessed relationships of air pollution with i) IR indexes, ii) ceramide metabolism, and iii) DNA methylation. Mediation analysis was subsequently performed to evaluate the potential mediating effect of DNA methylation in the association between air pollution and ceramide metabolism. PM and O were associated with elevated IR. Specifically, each 10 μg/m increase in PM and O at lag0-12 h significantly increased triglyceride‑glucose index (TyG index) and TyG-BMI (TyG - Body mass index) by 0.88%, 0.89% and 0.26%, 0.26%, respectively. Furthermore, levels of eight ceramides were altered by air pollution exposure, and nine methylated CpG sites in inflammation genes mediated the effects of air pollution on ceramide metabolism. Our findings imply the existence of a novel mechanism connecting air pollution to IR.
胰岛素抵抗（IR）与空气污染有关，是早发性 2 型糖尿病（T2DM）的初始阶段。虽然神经酰胺代谢在 IR 发病机制中起着重要作用，但空气污染对这一过程及其机制的影响仍不清楚。我们在中国武汉招募了 18-30 岁的年轻人参加一项面板研究。使用个人便携式设备和固定监测站，我们跟踪了空气动力学直径≤2.5µm 的颗粒物（PM）和臭氧（O）水平。基于液相色谱/质谱（LC-MS）的代谢组学定量了神经酰胺代谢，Illumina Infinium Human Methylation 850 kBeadChip 测定了脱氧核糖核酸（DNA）甲基化。线性混合效应模型评估了空气污染与 i）IR 指标、ii）神经酰胺代谢和 iii）DNA 甲基化的关系。随后进行了中介分析，以评估 DNA 甲基化在空气污染和神经酰胺代谢之间关联中的潜在中介作用。PM 和 O 与 IR 升高有关。具体而言，PM 和 O 在滞后 0-12 小时每增加 10μg/m，甘油三酯-葡萄糖指数（TyG 指数）和 TyG-BMI（TyG-体重指数）分别显著增加 0.88%、0.89%和 0.26%、0.26%。此外，八种神经酰胺的水平因空气污染暴露而改变，炎症基因中九个甲基化 CpG 位点介导了空气污染对神经酰胺代谢的影响。我们的研究结果表明，存在一种将空气污染与 IR 联系起来的新机制。
