PUBLICATION
Metabolic regulation by the PGC-1α and PGC-1β coactivators in larval zebrafish (Danio rerio)
- Authors
- Northam, C., LeMoine, C.M.R.
- ID
- ZDB-PUB-190422-21
- Date
- 2019
- Source
- Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 234: 60-67 (Journal)
- Registered Authors
- Keywords
- Citrate synthase, ERRĪ±, Lipid oxidation, Mitochondria, NRF-1, PPAR
- MeSH Terms
-
- Animals
- Carnitine O-Palmitoyltransferase/genetics
- Electron Transport Complex IV/metabolism
- Energy Metabolism/genetics*
- Gene Expression Regulation/genetics
- Larva/genetics
- Larva/growth & development
- Morpholinos/genetics
- Oxidation-Reduction
- Oxygen Consumption/genetics
- Receptors, Estrogen/genetics
- Transcription Factors/genetics*
- Zebrafish/genetics*
- Zebrafish Proteins/genetics*
- PubMed
- 31004809 Full text @ Comp. Biochem. Physiol. A Mol. Integr. Physiol.
Citation
Northam, C., LeMoine, C.M.R. (2019) Metabolic regulation by the PGC-1α and PGC-1β coactivators in larval zebrafish (Danio rerio). Comparative biochemistry and physiology. Part A, Molecular & integrative physiology. 234:60-67.
Abstract
The peroxisome proliferator activated receptor γ coactivator-1 (PGC-1) family is composed of three coactivators whose role in regulating mammalian bioenergetics regulation is clear, but is much less certain in other vertebrates. Current evidence suggests that in fish, PGC-1α and PGC-1β may exhibit much less redundancy in the control of fatty acid oxidation and mitochondrial biogenesis compared to mammals. To assess these roles directly, we knocked down PGC-1α and PGC-1β expression with morpholinos in zebrafish embryos, and we investigated the resulting molecular and physiological phenotypes. First, we found no effects of either morpholinos on larval hatching, heart rates and oxygen consumption over the first few days of development. Next, at 3 days post fertilization (dpf), we confirmed by real time PCR a specific knock down of both coactivators, that resulted in a significant reduction in the transcript levels of citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase (HOAD), and medium-chain acyl-coenzyme A dehydrogenase (MCAD) in both morphant groups. However, there was no effect on transcription factors' gene expression except for a marked reduction in estrogen related receptor α (ERRα) transcripts in PGC-1α morphants. Finally, we assessed whole embryonic enzyme activity for CS, cytochrome oxidase (COX), HOAD and carnitine palmitoyltransferase I (CPT-1) at 4 dpf. The only significant effect of the knockdown was a reduced CS activity in PGC-1α morphants and a counterintuitive increase of cytochrome oxidase activity in PGC-1β morphants. Overall, our results indicate that in larval zebrafish, PGC-1α and PGC-1β both play a role in regulating expression of important mitochondrial genes potentially through ERRα.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping