Metabolic regulation by the PGC-1α and PGC-1β coactivators in larval zebrafish (Danio rerio)
| Autor: | Caleb Northam, Christophe M. R. LeMoine |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Morpholino Physiology Peroxisome proliferator-activated receptor Biology Biochemistry Morpholinos Electron Transport Complex IV 03 medical and health sciences 0302 clinical medicine Oxygen Consumption Lipid oxidation Cytochrome c oxidase Animals Molecular Biology Zebrafish chemistry.chemical_classification Gene knockdown Carnitine O-Palmitoyltransferase Morphant Zebrafish Proteins Cell biology 030104 developmental biology chemistry Mitochondrial biogenesis Gene Expression Regulation Receptors Estrogen Larva biology.protein Carnitine palmitoyltransferase I Energy Metabolism Oxidation-Reduction 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Comparative biochemistry and physiology. Part A, Molecularintegrative physiology. 234 |
| ISSN: | 1531-4332 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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