Zebrafish Alcoholic Liver Disease Models

Alcoholic liver disease (ALD), caused by excessive alcohol consumption, is one of the most common causes of liver-related morbidity and mortality. ALD progresses from hepatic steatosis, steatohepatitis, fibrosis, cirrhosis, and eventually to hepatocellular carcinoma. It has been shown that zebrafish livers contain the major cell types found in mammalian livers and exhibit similar pathogenic responses to environmental insults and genetic mutations. Acute and chronic ethanol treatment can induce hepatic steatosis in larval and adult zebrafish, respectively, as reported by multiple research groups.

Oral alcohol only induces hepatic steatosis in rodent models, whereas a second injury is required for the development of inflammation and fibrosis. Zebrafish larvae are well suited for studying the effects of acute alcohol exposure because alcohol can be added to water without causing death. Genes and pathways essential for alcohol metabolism are highly conserved in zebrafish, which readily absorb and metabolize alcohol as early as 4 days after fertilization. Furthermore, zebrafish have analogs of ADH1 and CYP2E1 capable of metabolizing ethanol. Treatment of zebrafish larvae with pharmacological inhibitors of ADH1 and CYP2E1 blocks ethanol-induced hepatic steatosis.

Fig.1 Acute ethanol treatment causes hepatic steatosis in larval zebrafish.

Our Zebrafish Alcoholic Liver Disease Models

Creative Biogene's zebrafish alcohol injury model is achieved by exposing animals to ethanol in water through multiple routes, including the gastrointestinal tract, gills, and skin. We exposed 4-day-old zebrafish larvae to 2% ethanol for just 24 hours was sufficient to induce steatosis, angiogenesis, macrophage recruitment, and hepatic stellate cell activation. One day after removal of ethanol, the number of macrophages increased in treated livers, accompanied by increased hepatic angiogenesis and hepatic stellate cell proliferation. Furthermore, we have shown that adult zebrafish develop steatosis, steatohepatitis, and fibrosis when they are continuously reared in 1% ethanol for a long period of time.

Our zebrafish models can be used not only to study the initial response mechanisms of macrophages, endothelial cells, and hepatic stellate cells to the addition and removal of ethanol, but also to accelerate the development of therapies for acute and chronic alcoholic liver disease. If you are interested in the zebrafish alcoholic liver disease model, please feel free to contact us.

Advantages

• High-throughput gene and drug screening
• Rapidly perform reverse and forward genetic screening
• Track labeled cells in in vivo imaging analysis
• Labeling individual hepatocyte types using a transgenic fluorescent reporter strain, enabling real-time tracking of their morphology and behavior during development and injury

References

1. Shwartz A, Goessling W, Yin C. Macrophages in Zebrafish Models of Liver Diseases. Front Immunol. 2019, 10:2840.
2. Pham DH, Zhang C, Yin C. Using zebrafish to model liver diseases-Where do we stand?. Curr Pathobiol Rep. 2017, 5(2):207-221.

For research use only. Not intended for any clinical use.