PUBLICATION
Strategy of Hepatic Metabolic Defects Induced by beclin1 Heterozygosity in Adult Zebrafish
- Authors
- Mawed, S.A., He, Y., Zhang, J., Mei, J.
- ID
- ZDB-PUB-200229-2
- Date
- 2020
- Source
- International Journal of Molecular Sciences 21(4): (Journal)
- Registered Authors
- Mei, Jie
- Keywords
- PI3K/AKT, apoptosis, autophagy, beclin1, liver metabolism
- MeSH Terms
-
- Animals
- Apoptosis/genetics
- Autophagy/genetics
- Autophagy-Related Protein 7/genetics
- Autophagy-Related Protein 7/metabolism
- Beclin-1/genetics
- Beclin-1/metabolism*
- Carbohydrate Metabolism
- Cell Proliferation/genetics
- Hepatocytes/metabolism*
- Heterozygote
- Lipid Metabolism*
- Liver Diseases/genetics
- Liver Diseases/metabolism*
- Male
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 32102330 Full text @ Int. J. Mol. Sci.
Citation
Mawed, S.A., He, Y., Zhang, J., Mei, J. (2020) Strategy of Hepatic Metabolic Defects Induced by beclin1 Heterozygosity in Adult Zebrafish. International Journal of Molecular Sciences. 21(4):.
Abstract
Hepatic disorders have been increasing in recent years because of high carbohydrate diets. Hepatocytes depend mainly on the basal autophagy to maintain hepatic glucose/lipid homeostasis in mammals. However, the regulatory mechanisms of autophagy in hepatic energy metabolism are still unknown in fish species. Accordingly, mutant zebrafish lines of autophagy-related genes beclin1 and atg7 were generated by CRISPR/Cas9 gene-editing technology. Interestingly, unlike atg7+/-, male beclin1+/- zebrafish displayed liver defects in the morphology and histology, including abnormal hepatocyte proliferation, hemorrhagic and inflammatory phenotypes. A significant decrease in hepatocyte glycogen and an increase in hepatocyte lipids were detected in the histological assay that coincidence with the hepatic gene expression. Meanwhile, loss of heterozygosity for beclin1 creates a suitable microenvironment for hepatic tumorigenesis via phosphorylation of Akt kinase, which in turn affects liver autophagy. The reduction in autophagy activity in male beclin1+/- liver leads to a disturbance in the glucose/lipid metabolism and negatively regulates apoptosis accompanied by the induction of cellular proliferation and acute inflammatory response. Our findings highlight an important role of beclin1 in zebrafish liver development and energy metabolism, suggesting the crucial role of autophagy in maintaining homeostasis of the nutrient metabolism in fish species.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping