PUBLICATION
Increase of hepatic fat accumulation by liver specific expression of Hepatitis B virus X protein in zebrafish
- Authors
- Shieh, Y.S., Chang, Y.S., Hong, J.R., Chen, L.J., Jou, L.K., Hsu, C.C., and Her, G.M.
- ID
- ZDB-PUB-100427-20
- Date
- 2010
- Source
- Biochimica et biophysica acta. Molecular and cell biology of lipids 1801(7): 721-730 (Journal)
- Registered Authors
- Her, Guor Muor, Hong, Jiann-Ruey
- Keywords
- Hepatitis B virus X protein, Fatty liver disease, Non-alcoholic steatohepatitis, Liver degeneration, Transgenic zebrafish, GFP
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Apoptosis/genetics
- Disease Models, Animal
- Fatty Acids/biosynthesis*
- PubMed
- 20416398 Full text @ BBA Molecular and Cell Biology of Lipids
Abstract
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 approximately 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-alpha, SREBP1, ChREBP and PPAR-gamma, 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping