DNA methylation mediates the effects of PM2.5 and O3 on ceramide metabolism: A novel mechanistic link between air pollution and insulin resistance.
J Hazard Mater
; 469: 133864, 2024 May 05.
Article
de En
| MEDLINE
| ID: mdl-38457969
ABSTRACT
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 (PM2.5) and Ozone (O3) 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. PM2.5 and O3 were associated with elevated IR. Specifically, each 10 µg/m3 increase in PM2.5 and O3 at lag0-12 h significantly increased triglycerideglucose 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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Insulinorésistance
/
Diabète de type 2
/
Polluants atmosphériques
/
Pollution de l'air
Limites:
Adult
/
Humans
Langue:
En
Journal:
J Hazard Mater
Sujet du journal:
SAUDE AMBIENTAL
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine