PUBLICATION
A New In Vivo Zebrafish Bioassay Evaluating Liver Steatosis Identifies DDE as a Steatogenic Endocrine Disruptor, Partly through SCD1 Regulation
- Authors
- Le Mentec, H., Monniez, E., Legrand, A., Monvoisin, C., Lagadic-Gossmann, D., Podechard, N.
- ID
- ZDB-PUB-230226-67
- Date
- 2023
- Source
- International Journal of Molecular Sciences 24(4): (Journal)
- Registered Authors
- Keywords
- DDE, NAFLD, bioassay, endocrine disruptor compounds, liver steatosis, zebrafish larvae
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Endocrine Disruptors*/pharmacology
- Larva/metabolism
- Liver/metabolism
- Non-alcoholic Fatty Liver Disease*/metabolism
- Zebrafish/genetics
- PubMed
- 36835354 Full text @ Int. J. Mol. Sci.
Citation
Le Mentec, H., Monniez, E., Legrand, A., Monvoisin, C., Lagadic-Gossmann, D., Podechard, N. (2023) A New In Vivo Zebrafish Bioassay Evaluating Liver Steatosis Identifies DDE as a Steatogenic Endocrine Disruptor, Partly through SCD1 Regulation. International Journal of Molecular Sciences. 24(4):.
Abstract
Non-alcoholic fatty liver disease (NAFLD), which starts with liver steatosis, is a growing worldwide epidemic responsible for chronic liver diseases. Among its risk factors, exposure to environmental contaminants, such as endocrine disrupting compounds (EDC), has been recently emphasized. Given this important public health concern, regulation agencies need novel simple and fast biological tests to evaluate chemical risks. In this context, we developed a new in vivo bioassay called StAZ (Steatogenic Assay on Zebrafish) using an alternative model to animal experimentation, the zebrafish larva, to screen EDCs for their steatogenic properties. Taking advantage of the transparency of zebrafish larvae, we established a method based on fluorescent staining with Nile red to estimate liver lipid content. Following testing of known steatogenic molecules, 10 EDCs suspected to induce metabolic disorders were screened and DDE, the main metabolite of the insecticide DDT, was identified as a potent inducer of steatosis. To confirm this and optimize the assay, we used it in a transgenic zebrafish line expressing a blue fluorescent liver protein reporter. To obtain insight into DDE's effect, the expression of several genes related to steatosis was analyzed; an up-regulation of scd1 expression, probably relying on PXR activation, was found, partly responsible for both membrane remodeling and steatosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping