Overexpression of gankyrin induces liver steatosis in zebrafish (Danio rerio)

Guor Mour Her, Chia Chun Hsu, Jiann Ruey Hong, Chi Yu Lai, Meng Chieh Hsu, Hsi Wen Pang, Sheng Kai Chan, Wan Yu Pai

Research output: Contribution to journalArticle

49 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)536-548
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1811
Issue number9
DOIs
Publication statusPublished - 2011 Sep 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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