PUBLICATION
Enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (ehhadh) is essential for production of DHA in zebrafish
- Authors
- Yang, G., Sun, S., He, J., Wang, Y., Ren, T., He, H., Gao, J.
- ID
- ZDB-PUB-230103-3
- Date
- 2022
- Source
- Journal of Lipid Research 64(3): 100326 (Journal)
- Registered Authors
- Keywords
- "Sprecher" pathway, PPAR signaling pathway, PUFA synthesis, SREBF signaling pathway, docosahexaenoic acid synthesis, fatty acids, freshwater fish, liver, peroxisome β-oxidation, transgenic zebrafish
- MeSH Terms
-
- 3-Hydroxyacyl CoA Dehydrogenases/genetics
- 3-Hydroxyacyl CoA Dehydrogenases/metabolism
- 3-Hydroxyacyl CoA Dehydrogenases/pharmacology
- Acetyltransferases/metabolism
- Animals
- Enoyl-CoA Hydratase*/genetics
- Enoyl-CoA Hydratase*/metabolism
- Enoyl-CoA Hydratase*/pharmacology
- Liver/metabolism
- Peroxisomal Bifunctional Enzyme/metabolism
- Peroxisomes/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 36592657 Full text @ J. Lipid Res.
Citation
Yang, G., Sun, S., He, J., Wang, Y., Ren, T., He, H., Gao, J. (2022) Enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (ehhadh) is essential for production of DHA in zebrafish. Journal of Lipid Research. 64(3):100326.
Abstract
Compared with other species, freshwater fish are more capable of synthesizing docosahexaenoic acid (DHA) via same biosynthetic pathways. Freshwater fish have a "Sprecher" pathway to biosynthesize DHA in a peroxisome-dependent manner. Enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (ehhadh) is involved in the hydration and dehydrogenation reactions of fatty acid β-oxidation in peroxisomes. However, the role of ehhadh in the synthesis of DHA in freshwater fish remains largely unclear. In this study, the knockout of ehhadh significantly inhibited DHA synthesis in zebrafish. Liver transcriptome analysis showed that ehhadh deletion significantly inhibited SREBF and PPAR signaling pathways and decreased the expression of PUFA synthesis-related genes. Our results from analysis of transgenic zebrafish (Tg:ehhadh) showed that ehhadh overexpression significantly increased the DHA content in the liver and significantly up-regulated the expression of genes related to PUFA synthesis. In addition, the DHA content in the liver of Tg:ehhadh fed with linseed oil (LO) was significantly higher than that of wildtype, but the expression of PUFA synthesis-related genes fads2 and elovl2 were significantly lower, indicating that ehhadh had a direct effect on DHA synthesis. In conclusion, our results showed that ehhadh was essential for DHA synthesis in the "Sprecher" pathway, and ehhadh overexpression could promote DHA synthesis. This study provides insight into the role of ehhadh in freshwater fish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping