ZFIN ID: ZDB-PUB-110706-11
Overexpression of gankyrin induces liver steatosis in zebrafish (Danio rerio)
Her, G.M., Hsu, C.C., Hong, J.R., Lai, C.Y., Hsu, M.C., Pang, H.W., Chan, S.K., and Pai, W.Y.
Date: 2011
Source: Biochimica et biophysica acta. Molecular and cell biology of lipids   1811(9): 536-48 (Journal)
Registered Authors: Her, Guor Muor, Hong, Jiann-Ruey
Keywords: hepatic steatosis, lipid accumulation, lipid metabolism, microRNA, transgenic zebrafish, liver hypoplasia
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Fatty Liver/metabolism*
  • Fatty Liver/pathology
  • Female
  • Humans
  • Lipid Metabolism
  • Liver/pathology
  • Liver/physiology
  • Male
  • MicroRNAs/metabolism
  • Molecular Sequence Data
  • Proteasome Endopeptidase Complex/genetics
  • Proteasome Endopeptidase Complex/metabolism*
  • Proto-Oncogene Proteins/genetics
  • Proto-Oncogene Proteins/metabolism*
  • Zebrafish/anatomy & histology*
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 21722753 Full text @ BBA Molecular and Cell Biology of Lipids
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ABSTRACT
Gankyrin is a small ankyrin-repeat protein that previous research has confirmed to be overexpressed in hepatocellular carcinoma (HCC). Although relevant literature has reported on gankyrin functions in cellular proliferation and tumorigenesis, the exact role of gankyrin is poorly understood in animal model systems. This study analyzed hepatic lipid accumulation in gankyrin transgenic (GK) zebrafish. Bromodeoxyuridine (BrdU)-positive cells were predominantly increased in the liver bud of GK larvae, indicating that gankyrin functionally promoted cell proliferation at the larval stage in GK fish. However, over 90% of the viable GK adults showed an increased lipid content, leading in turn to liver steatosis. Liver histology and oil red O staining also indicated the accumulation of fatty droplets in GK fish, consistent with the specific pathological features of severe steatosis. Molecular analysis revealed that gankyrin overexpression induced hepatic steatosis and modulated the expression profiles of four hepatic microRNAs, miR-16, miR-27b, miR-122, and miR-126, and 22 genes involved in lipid metabolism. Moreover, significantly increased hepatic cell apoptosis resulted in liver damage in GK adults, leading to liver failure and death after approximately 10 months. This study is the first to report gankyrin as a potential link between microRNAs and liver steatosis in zebrafish.
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