The role of endoplasmic reticulum stress in Atrazine-induced hepatic lipid accumulation

Atrazine (ATR) is an extensively applied triazine herbicide which belongs to the persistent environmental endocrine disruptors. ATR is capable of penetrating the body and disrupting lipid metabolism, but its underlying mechanism is still unclear. L02 hepatocytes were exposed to ATR (0 (Con), 10, 50, 100 μM) and 0.02 % DMSO (VCon) for 24 h. Lipid levels were measured using colorimetry. The lipid droplet accumulation level and detection of Ca^2 + levels by fluorescent staining. Real-Time PCR and Western blot were used to measure mRNA and protein levels. The results showed that groups treated with ATR exhibited elevated levels of lipid. Both intracellular lipid droplet accumulation and Ca²⁺ levels increased proportionally with higher ATR dosages. Additionally, the levels of genes linked to lipid metabolism (DGAT2, ACC1, PPARγ, and SCD1) were upregulated. Endoplasmic reticulum stress (ERS) was triggered, leading to augmented gene expression in the IRE1α/XBP1 signaling pathway, as well as enhanced expression of GRP78 and GRP94. ERS was inhibited by 4-phenylbutyric acid (4-PBA), IRE1α was silenced by lentivirus transfection. Notably, the upregulation of IRE1α, XBP1, GRP78, and GRP94, alongside the ATR-induced lipid elevations, were significantly reversed upon ERS inhibition or IRE1α gene silencing. This study demonstrated that ATR exposure caused ERS in L02 hepatocytes, and induced lipid metabolism disorders by activation the key ERS signal pathway IRE1α/XBP1, resulting in hepatic lipid accumulation.