Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), a novel brominated
flame retardant, can potentially cause
lipid metabolism disorder; however, its
biological effects on
lipid homeostasis remain unknown. We investigated its ability to cause
nonalcoholic fatty liver disease (
NAFLD) in zebrafish. Female zebrafish were fed a high-fat diet (HFD, 24% crude fat) or normal diet (ND, 6% crude fat), and exposed to TBPH (0.02, 2.0 μM) for 2 weeks. Consequently, HFD-fed fish showed a higher measured concentration of TBPH than ND-fed fish. Further, TBPH-treated fish in the HFD group showed higher hepatic
triglyceride levels and steatosis. In comparison to ND-fed fish, treating HFD-fed fish with TBPH led to an increase in the concentration of several proinflammatory markers (e.g., TNF-α, IL-6); TBPH exposure also caused oxidative stress. In addition, the
mRNA levels of genes encoding
peroxisome proliferator-activated receptors were increased, and the transcription of genes involved in
lipid synthesis, transport, and oxidation was upregulated in both ND- and HFD-fed fish. Both the ND and HFD groups also showed demethylation of the
peroxisome proliferator-activated receptor-γ coactivator 1-α gene promoter, accompanied by the upregulation of tet1 and tet2 transcription. To summarize, we found that TBPH amplified the disruption of
lipid homeostasis in zebrafish, leading to the enhancement of diet-induced
NAFLD progression.