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
  • Heterozygote
  • Hepatocytes/metabolism*
  • Lipid Metabolism*
  • Carbohydrate Metabolism
  • Apoptosis/genetics
  • Autophagy-Related Protein 7/genetics
  • Autophagy-Related Protein 7/metabolism
  • Cell Proliferation/genetics
  • Animals
  • Male
  • Autophagy/genetics
  • Beclin-1/genetics
  • Beclin-1/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Liver Diseases/genetics
  • Liver Diseases/metabolism*
(all 19)
PubMed
32102330 Full text @ Int. J. Mol. Sci.
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
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
atg7hza54/+ (AB)standard conditionsAdult
atg7hza54/+ (AB)standard conditionsAdult
atg7hza54/+ (AB)standard conditionsAdult
atg7hza54/+ (AB)standard conditionsAdult
atg7hza54/+ (AB)standard conditionsAdult
atg7hza54/hza54 (AB)standard conditionsProtruding-mouth to Days 7-13
atg7hza55/+ (AB)standard conditionsAdult
atg7hza55/+ (AB)standard conditionsAdult
atg7hza55/+ (AB)standard conditionsAdult
atg7hza55/+ (AB)standard conditionsAdult
1 - 10 of 64
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hza54
    		Small Deletion
    hza55
      		Small Deletion
      hza56
        		Small Deletion
        1 - 3 of 3
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        Human Disease / Model
        Human Disease Fish Conditions Evidence
        hepatocellular carcinomabecn1hza56/+ (AB)standard conditionsTAS
        1 - 1 of 1
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        Sequence Targeting Reagents
        Target Reagent Reagent Type
        atg7CRISPR2-atg7CRISPR
        becn1CRISPR1-becn1CRISPR
        1 - 2 of 2
        Show
        Fish
        Fish
        AB
        atg7hza54/hza54 (AB)
        atg7hza54/+ (AB)
        atg7hza55/hza55 (AB)
        atg7hza55/+ (AB)
        becn1hza56/hza56 (AB)
        becn1hza56/+ (AB)
        1 - 7 of 7
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        Antibodies
        Orthology
        No data available
        Engineered Foreign Genes
        No data available
        Mapping
        No data available
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        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):.