Bis(2-ethylhexyl)-tetrabromophthalate induces zebrafish obesity by altering the brain-gut axis and intestinal microbial composition

Multiple environmental stressors, including chemicals termed obesogens, contribute to the susceptibility of organisms to obesity. Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), a novel brominated flame retardant, is an environmental contaminant that may disrupt lipid metabolism. However, the risk of TBPH leading to obesity remains unknown. Herein, adult female zebrafish fed a normal-fat diet (NFD) or high-fat diet (HFD) were exposed to 0, 0.02 and 2.0 μM TBPH for 6 weeks. The results showed that chronic TBPH exposure lead to significant weight gain, adipocyte hypertrophy, and subcutaneous fat accumulation, which could be enhanced by HFD feeding. HFD individuals also showed significant visceral fat accumulation. Transcription of the main adipokines regulating lipid metabolism associated with the brain-gut axis were significantly affected by TBPH, especially leptin (brain) and adiponectin (intestine). Additionally, peroxisome proliferator-activated nuclear receptor gamma (PPAR-γ) was significantly upregulated in intestine. TBPH increased the abundance of Firmicutes and Bacteroidetes in the gut microbiota in both NFD and HFD groups, resulting in obesity. Interestingly, population diversity analysis indicated that TBPH alone had a comparable impact on gut microbiota composition to that of HDF controls. Thus, TBPH increased the susceptibility of female zebrafish to obesity by disrupting brain-gut axis regulation and gut microbial composition, leading to enhanced fat accumulation under HFD conditions.