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FOXO3/Rab7-Mediated Lipophagy and Its Role in Zn-Induced Lipid Metabolism in Yellow Catfish (Pelteobagrus fulvidraco)
- Source :
- Genes, Vol 15, Iss 3, p 334 (2024)
- Publication Year :
- 2024
- Publisher :
- MDPI AG, 2024.
-
Abstract
- Lipophagy is a selective autophagy that regulates lipid metabolism and reduces hepatic lipid deposition. However, the underlying mechanism has not been understood in fish. In this study, we used micronutrient zinc (Zn) as a regulator of autophagy and lipid metabolism and found that Ras-related protein 7 (rab7) was involved in Zn-induced lipophagy in hepatocytes of yellow catfish Pelteobagrus pelteobagrus. We then characterized the rab7 promoter and identified binding sites for a series of transcription factors, including Forkhead box O3 (FOXO3). Site mutation experiments showed that the −1358/−1369 bp FOXO3 binding site was responsible for Zn-induced transcriptional activation of rab7. Further studies showed that inhibition of rab7 significantly inhibited Zn-induced lipid degradation by lipophagy. Moreover, rab7 inhibitor also mitigated the Zn-induced increase of cpt1α and acadm expression. Our results suggested that Zn exerts its lipid-lowering effect partly through rab7-mediated lipophagy and FA β-oxidation in hepatocytes. Overall, our findings provide novel insights into the FOXO3/rab7 axis in lipophagy regulation and enhance the understanding of lipid metabolism by micronutrient Zn, which may help to reduce excessive lipid accumulation in fish.
- Subjects :
- rab7
FOXO3
promoter analysis
lipophagy
lipid metabolism
Zn
Genetics
QH426-470
Subjects
Details
- Language :
- English
- ISSN :
- 15030334 and 20734425
- Volume :
- 15
- Issue :
- 3
- Database :
- Directory of Open Access Journals
- Journal :
- Genes
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.4cdd81fffe644effb6b1102227caf5f7
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/genes15030334