PUBLICATION
Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate Enhances foxo1-Mediated Lipophagy to Remodel Lipid Metabolism in Zebrafish Liver
- Authors
- Zhou, Y., Li, F., Fu, K., Zhang, Y., Zheng, N., Tang, H., Xu, Z., Luo, L., Han, J., Yang, L., Zhou, B.
- ID
- ZDB-PUB-240301-9
- Date
- 2024
- Source
- Environmental science & technology 58(10): 4581-4593 (Journal)
- Registered Authors
- Yang, LiHua, Zhou, BingSheng
- Keywords
- bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate, foxo1, hepatic lipid metabolism, lipophagy, multiomics analysis, transgenic zebrafish
- MeSH Terms
-
- Animals
- Autophagy
- Lipid Metabolism*
- Lipids
- Liver/metabolism
- Zebrafish*
- PubMed
- 38422554 Full text @ Env. Sci. Tech.
Citation
Zhou, Y., Li, F., Fu, K., Zhang, Y., Zheng, N., Tang, H., Xu, Z., Luo, L., Han, J., Yang, L., Zhou, B. (2024) Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate Enhances foxo1-Mediated Lipophagy to Remodel Lipid Metabolism in Zebrafish Liver. Environmental science & technology. 58(10):4581-4593.
Abstract
An emerging environmental contaminant, bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), can bioaccumulate in the liver and affect hepatic lipid metabolism. However, the in-depth mechanism has yet to be comprehensively explored. In this study, we utilized transgenic zebrafish Tg (Apo14: GFP) to image the interference of TBPH on zebrafish liver development and lipid metabolism at the early development stage. Using integrated lipidomic and transcriptomic analyses to profile the lipid remodeling effect, we uncovered the potential effects of TBPH on lipophagy-related signaling pathways in zebrafish larvae. Decreased lipid contents accompanied by enhanced lipophagy were confirmed by the measurements of Oil Red O staining and transmission electron microscopy in liver tissues. Particularly, the regulatory role of the foxo1 factor was validated via its transcriptional inhibitor. Double immunofluorescence staining integrated with biochemical analysis indicated that the enhanced lipophagy and mitochondrial fatty acid oxidation induced by TBPH were reversed by the foxo1 inhibitor. To summarize, our study reveals, for the first time, the essential role of foxo1-mediated lipophagy in TBPH-induced lipid metabolic disorders and hepatoxicity, providing new insights for metabolic disease studies and ecological health risk assessment of TBPH.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping