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.
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