PUBLICATION
Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate affects lipid metabolism in zebrafish larvae via DNA methylation modification
- Authors
- Guo, W., Han, J., Wu, S., Shi, X., Wang, Q., Zhou, B.
- ID
- ZDB-PUB-191206-27
- Date
- 2019
- Source
- Environmental science & technology 54(1): 355-363 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- PPAR gamma
- Lipid Metabolism
- DNA Methylation*
- Animals
- Larva
- Zebrafish*
- Molecular Docking Simulation
- PubMed
- 31804803 Full text @ Env. Sci. Tech.
Citation
Guo, W., Han, J., Wu, S., Shi, X., Wang, Q., Zhou, B. (2019) Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate affects lipid metabolism in zebrafish larvae via DNA methylation modification. Environmental science & technology. 54(1):355-363.
Abstract
Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) is a ubiquitous environmental contaminant, but its toxicity is not fully understood. Accordingly, we investigated the effects of TBPH and its metabolite, mono-(2-ethyhexyl) tetrabromophthalate (TBMEHP), on lipid metabolism using a zebrafish model. Molecular docking study revealed that TBPH and TBMEHP bind to zebrafish peroxisome proliferator-activated receptor γ (PPARγ), with binding energies similar to rosiglitazone, a PPARγ agonist. Zebrafish embryos 0.75 h post-fertilization (hpf) were exposed to TBPH (0.2~2,000 nM) or TBMEHP (0.2~2,000 nM) until 72 hpf, and their effects on PPARγ-mediated lipid metabolism were evaluated. Significant regional DNA demethylation of the PPARγ promoter was observed in the larvae at 72 hpf. Demethylation of the PPARγ promoter accompanied by upregulation of tet1 and tet2 transcription caused upregulation of PPARγ transcription and certain downstream genes involved in lipid lipolysis, transport, and metabolism. The triglyceride and total cholesterol concentrations in the larvae were significantly reduced following exposure to TBPH or TBMEHP. Furthermore, significant increases in the whole ATP content and locomotor activity in the 120 hpf larvae were observed. The overall results suggest that both TBPH and TBMEHP affect methylation of the PPARγ promoter, subsequently influencing larvae lipid metabolism via the PPARγ signaling pathway and disrupting energy homeostasis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping