Diesel exhaust induces hepatic steatosis by activating the aryl hydrocarbon receptor/CD36 pathway.

Diesel exhaust (DE) entering the environment poses a significant risk to public health, but the molecular mechanisms of DE-induced metabolic disorders remain largely unknown. Here we elucidated the impacts of DE exposure on hepatic lipid metabolism using a range of cohort, in vivo, and in vitro approaches. The cohort study revealed altered liver function indices of diesel engine testers (DETs) compared to those of non-DETs and with increasing exposure duration. Mice exposed to DE via whole-body exposure system developed hepatic steatosis, which coincided with an upregulation of the fatty acid transporter CD36, and a marked increase in long-chain fatty acids. Mechanistically, enhanced CD36 expression was predominantly related to the activation of aryl hydrocarbon receptor (AHR). Notably, treatment with organic extract of diesel exhaust particulate (DEP-OE) up-regulated the AHR/CD36 signaling pathway, and led to lipid accumulation in primary mouse hepatocytes. Both effects were markedly diminished by AHR and CD36 knockdown. Finally, we show that targeted inhibition of AHR alleviated DE-induced steatosis in mouse liver. Together, we demonstrate that the organic components of DE cause hepatic steatosis by activating the AHR/CD36 signaling pathway. Our research elucidates DE exposure risks and sheds new insights into the early prevention of diseases in DE-exposed populations.