PUBLICATION
Nonalcoholic Fatty Liver Disease Development in Zebrafish upon Exposure to Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate, a Novel Brominated Flame Retardant
- Authors
- Guo, W., Lei, L., Shi, X., Li, R., Wang, Q., Han, J., Yang, L., Chen, L., Zhou, B.
- ID
- ZDB-PUB-210504-12
- Date
- 2021
- Source
- Environmental science & technology 55(10): 6926-6935 (Journal)
- Registered Authors
- Yang, LiHua, Zhou, BingSheng
- Keywords
- DNA demethylation, TBPH, hepatic steatosis, lipid metabolism, nonalcoholic fatty liver disease, novel brominated flame retardant, zebrafish
- MeSH Terms
-
- Animals
- Female
- Flame Retardants*/toxicity
- Homeostasis
- Liver
- Non-alcoholic Fatty Liver Disease*/chemically induced
- Zebrafish
- PubMed
- 33938212 Full text @ Env. Sci. Tech.
Citation
Guo, W., Lei, L., Shi, X., Li, R., Wang, Q., Han, J., Yang, L., Chen, L., Zhou, B. (2021) Nonalcoholic Fatty Liver Disease Development in Zebrafish upon Exposure to Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate, a Novel Brominated Flame Retardant. Environmental science & technology. 55(10):6926-6935.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping