ARMMs modulate Notch signaling pathway in DBDPE-induced liver lipid metabolism disorders: An in vivo and in vitro...

Decabromodiphenyl ethane (DBDPE) is a kind of commonly used novel brominated flame retardants, and widely exists in environments. DBDPE could be enriched in the liver, but its effects on lipid metabolism in liver and underlying mechanisms remain largely unknown. In the present study, firstly, we investigated the impact of DBDPE on the liver in rats and L02 cells. We found that DBDPE exposure could induce lipid metabolism disorders, up-regulate the expressions of Notch pathway genes, and promote Arrestin domain containing protein 1-mediated microvesicles (ARMMs)-derivation. Subsequently, siRNAs were used to inhibit the Notch pathway and the ARMMs-derivation in L02 cells respectively. It demonstrated that inhibition of Notch or ARMMs-derivation could reverse the lipid accumulation induced by DBDPE, and the inhibition of ARMMs-derivation could suppress the activation of the Notch pathway. Extracellular vesicles from L02 cells exposed to DBDPE co-culture with L02 cells confirmed that ARMMs can directly activate the Notch signaling pathway and induce lipid accumulation. In conclusion, our study is the first to explore the role of ARMMs in lipid metabolism disorders caused by environmental pollutants. We found that exposure to DBDPE increases the levels of ARMMs, which directly activates the Notch signaling pathway and triggers disruptions of liver lipid metabolism.