The combined impact of decabromodiphenyl ether and high fat exposure on non-alcoholic fatty liver disease in vivo and in vitro

Non-alcoholic fatty liver disease (NAFLD) is considered a public health concern. Decabromodiphenyl ether (BDE-209) and high fat (HF) exposure cause liver injury, yet the combined impact on NAFLD development remains unclear. HepG2 cells were incubated with BDE-209 or/and HF reagent (Csodium oleate/Csodium palmitate = 2/1) for establishing the in vitro model, while C57BL/6 mice fed BDE-209 or/and HF diet (HFD) was the in vivo model. Oil Red O staining and the determination of triglyceride, malondialdehyde, and reactive oxygen species (ROS) contents proved the elevated lipid accumulation and oxidative stress by the mixture of BDE-209 and HF in HepG2 cells, consistent in C57BL/6 mice. Importantly, the action analysis showed the synergistic effect between BDE-209 and HF, suggesting that the population preferring the HFD is more susceptible to BDE-209 to aggravate the progression of NAFLD. Further, the increased protein expression of sterol regulatory element-binding protein 1, fatty acid synthase, and stearoyl-CoA desaturase 1 was considered to be responsible for hepatic steatosis. The impairment of antioxidant system was reflected by the lower hepatic superoxide dismutase and glutathione transferase activities and reduced glutathione level, explaining the detected excessive ROS production. Besides, using high content analysis, the decline of mitochondrial mass and membrane potential, which was closed to the NAFLD pathogenesis, was also demonstrated in HepG2 cells.