Increase of hepatic fat accumulation by liver specific expression of Hepatitis B virus X protein in zebrafish

Yun Sheng Shieh, Yin Shan Chang, Jiann Ruey Hong, Li Je Chen, Luen Kuang Jou, Chia Chun Hsu, Guor Mour Her

研究成果: Article同行評審

55 引文 斯高帕斯(Scopus)

摘要

The pathogenesis of fatty liver disease remains largely unknown. Here, we assessed the importance of hepatic fat accumulation on the progression of hepatitis in zebrafish by liver specific expression of Hepatitis B virus X protein (HBx). Transgenic zebrafish lines, GBXs, which selectively express the GBx transgene (GFP-fused HBx gene) in liver, were established. GBX Liver phenotypes were evaluated by histopathology and molecular analysis of fatty acid (FA) metabolism-related genes expression. Most GBXs (66-81%) displayed obvious emaciation starting at 4 months old. Over 99% of the emaciated GBXs developed hepatic steatosis or steatohepatitis, which in turn led to liver hypoplasia. The liver histology of GBXs displayed steatosis, lobular inflammation, and balloon degeneration, similar to non-alcoholic steatohepatitis (NASH). Oil red O stain detected the accumulation of fatty droplets in GBXs. RT-PCR and Q-rt-PCR analysis revealed that GBx induced hepatic steatosis had significant increases in the expression of lipogenic genes, C/EBP-α, SREBP1, ChREBP and PPAR-γ, which then activate key enzymes of the de novo FA synthesis, ACC1, FAS, SCD1, AGAPT, PAP and DGAT2. In addition, the steatohepatitic GBX liver progressed to liver degeneration and exhibited significant differential gene expression in apoptosis and stress. The GBX models exhibited both the genetic and functional factors involved in lipid accumulation and steatosis-associated liver injury. In addition, GBXs with transmissible NASH-like phenotypes provide a promising model for studying liver disease.

原文English
頁(從 - 到)721-730
頁數10
期刊Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
1801
發行號7
DOIs
出版狀態Published - 2010 7月

All Science Journal Classification (ASJC) codes

  • 分子生物學
  • 細胞生物學

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