Lipid metabolism dysfunction and toxicity of BDE-47 exposure in white adipose tissue revealed by the integration of lipidomics and metabolomics.

2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is one of the main and toxic congeners of polybrominated diphenyl ether (PBDE) family and considered to be associated with the development of obesity. However, little is known about its direct metabolic alterations on white adipose tissue (WAT). In this study, we evaluated the impacts of BDE-47 exposure on WAT dysfunctions in mice fed with low-fat diet (LFD) or high-fat diet (HFD) by the integration analysis of mass spectrometry-based metabolomics and lipidomics. The results showed that BDE-47 exposure together with HFD intervention induced adipocyte hypertrophy and accelerated the weight gain of WAT, whereas no obvious effects were observed in mice fed with LFD. The combination of BDE-47 and HFD induced intolerable levels of metabolites in purine and glutathione metabolism pathways, sufficient to increase oxidative stress in WAT. Importantly, continuous exposure of BDE-47 in HFD -fed mice caused lipid metabolism dysfunction by promoting fatty acid uptake and de novo synthesis and suppressing β-oxidation, ultimately leading to the accumulation of saturated fatty acids, triglycerides in WAT. At the same time, BDE-47 increased inflammatory infiltration into WAT, consequently promoting the productions of cytokines, TNFα and IL-6, in HFD fed mice. It is found that dysfunction of lipid metabolism and increasing inflammation led to lipotoxicity in WAT and severe obesity in HFD mice. Taken together, our findings deepen the understanding of the obesogenic effect of BDE-47 and help identify new potential strategies for clarifying the molecular and metabolic mechanisms.