Atrazine Induces Hepatic Lipid Metabolism Disorder via BMP9/SMAD1/5-Mediated Iron Overload

Atrazine (ATR) is a widely used herbicide that can affect liver metabolism. ATR disrupts hepatic lipid metabolism, and iron homeostasis is closely associated with hepatic lipid regulation. The BMP9/SMAD1/5 signaling pathway plays an important role in maintaining iron homeostasis. Therefore, we investigated whether ATR-induced disruption of BMP9/SMAD1/5 signaling contributes to hepatic lipid accumulation by disturbing iron homeostasis. The research results show that in the liver of rats and L02 cells, ATR can cause lipid accumulation by down-regulating lipid metabolism-related proteins. ATR alters the expression of iron metabolism-related proteins, leading to iron accumulation in the liver and L02 cells. In addition, ATR exposure can inhibit the BMP9/SMAD1/5 pathway, causing iron overload in the liver. ATR-induced iron overload further exacerbated hepatic lipid metabolic dysfunction. The activation of the BMP9/SMAD1/5 signaling pathway can reduce intracellular iron accumulation induced by ATR and alleviate the increase in TC and TG levels. Overall, these findings suggested that ATR can induce iron overload by inhibiting the BMP9/SMAD1/5 pathway, thereby contributing to hepatic lipid accumulation. This provides new insights into the toxic mechanisms of ATR.