Risk assessment of the lipid metabolism-disrupting effects of nitro-PAHs

Nitro-polycyclic aromatic hydrocarbons (NPAHs) are of increasing global concern due to their ubiquitous occurrence and long-range transport in the environment. However, their potential metabolism-disrupting effects, especially nuclear receptor-related lipid disorders, are still poorly understood. Targeting estrogen receptor α (ERα), this study for the first time evaluated the lipid metabolic effects of NPAHs using in vitro and in vivo models. The results indicated that four of the five NPAHs tested exhibited significant ERα agonistic activities, and induced increased secretion of 17β-estradiol (E₂) in HepG2 cells. Furthermore, lipidomic analysis showed that exposure to the candidate NPAH (3-nitrofluoranthene, 3-NFA) led to elevated hepatic levels of triacylglycerols (TAGs) and cholesteryl esters (CEs). Importantly, the lipid overload induced by 3-NFA was verified in the livers of zebrafish larvae using Oil Red O staining. Additionally, significant increases in E₂ production and the expression levels of associated genes (17βHSD and C/EBP-α) further supported the involvement of the ERα signaling pathway in the lipid metabolic perturbation induced by 3-NFA. These results provide novel insight into the lipid metabolism-disrupting effects induced by NPAHs and may offer a better understanding of the environmental risks of NPAHs.