Work

The key metabolic signatures and biomarkers of polycyclic aromatic hydrocarbon-induced blood glucose elevation in chinese individuals exposed to diesel engine exhaust

Year: 2024

Type: article

Abstract: Due to the complexity of environmental exposure factors and the low levels of exposure in the general population, identifying the key environmental factors associated with diabetes and understanding their potential mechanisms present significant challenges. This study aimed to identify key polycyclic aromatic hydrocarbons (PAHs) contributing to increased fasting blood glucose (FBG) concentrations and to explore their potential metabolic mechanisms. We recruited a highly PAH-exposed diesel engine exhaust testing population and healthy controls. Our findings found a positive association between FBG concentrations and PAH metabolites, identifying 1-OHNa, 2-OHPh, and 9-OHPh as major contributors to the rise in FBG concentrations induced by PAH mixtures. Specifically, each 10 % increase in 1-OHNa, 2-OHPh, and 9-OHPh concentrations led to increases in FBG concentrations of 0.201 %, 0.261 %, and 0.268 %, respectively. Targeted metabolomics analysis revealed significant alterations in metabolic pathways among those exposed to high levels of PAHs, including sirtuin signaling, asparagine metabolism, and proline metabolism pathway. Toxic function analysis highlighted differential metabolites involved in various dysglycemia-related conditions, such as cardiac arrhythmia and renal damage. Mediation analysis revealed that 2-aminooctanoic acid mediated the FBG elevation induced by 2-OHPh, while 2-hydroxyphenylacetic acid and hypoxanthine acted as partial suppressors. Notably, 2-aminooctanoic acid was identified as a crucial intermediary metabolic biomarker, mediating significant portions of the associations between the multiple different structures of OH-PAHs and elevated FBG concentrations, accounting for 16.73 %, 10.84 %, 10.00 %, and 11.90 % of these effects for 1-OHPyr, 2-OHFlu, the sum concentrations of 2- and 9-OHPh, and the sum concentrations of total OH-PAHs, respectively. Overall, our study explored the potential metabolic mechanisms underlying the elevated FBG induced by PAHs and identified 2-aminooctanoic acid as a pivotal metabolic biomarker, presenting a potential target for intervention. The association between PAH exposure and fasting blood glucose (FBG) level were systematically explored in occupationally diesel engine exhaust exposed workers through metabolomics and multiple statistical models. Three key OH-PAHs (1-OHNa, 2-OHPh, and 9-OHPh) were identified as being strongly associated with elevated FBG concentrations. Metabolomics revealed that metabolic pathways (e.g., sirtuin signaling, asparagine metabolism, and proline metabolism pathways) were significantly altered after PAHs exposure. 2-aminooctanoic acid was identified as a crucial intermediary metabolic biomarker, mediating the associations between the concentrations of multiple OH-PAHs with different structures (and elevated FBG concentrations. Besides, we proposed a putative adverse outcome pathway, involving PAHs exposure induced the alternations in key metabolites, disruptions in metabolic pathways and contributing to elevated FBG concentration outcome finally. • High levels of PAH exposure were associated with elevated FBG, and three key OH-PAHs (1-OHNa, 2-OHPh, and 9-OHPh) were identified. • The sirtuin signaling, asparagine metabolism, and proline metabolism pathways were related to PAHs induced dysglycemia. • 2-Aminooctanoic acid as a novel biomarker mediated the association between different structural OH-PAHs and elevated FBG concentrations.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2024.116997