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Hepatitis C virus induces the cannabinoid receptor 1
David van der Poorten1, Mahsa Shahidi, Enoch Tay
1Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Sydney, Australia.
Plos One
|September 24, 2010
Summary
Cannabinoid receptor 1 (CB1) is elevated in chronic hepatitis C (CHC) patients, correlating with liver steatosis, especially in genotype 3. Hepatitis C virus (HCV) infection induces CB1 expression.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- Hepatic CB1 receptor activation links to liver steatosis and fibrosis in experimental models.
- Chronic hepatitis C (CHC) is associated with insulin resistance, steatosis, and metabolic disturbances.
- CB1 expression in CHC patients remains uncharacterized.
Purpose of the Study:
- To assess CB1 receptor expression in CHC patients.
- To explore associations between CB1 expression and CHC disease parameters.
- To investigate the role of Hepatitis C virus (HCV) in CB1 induction.
Main Methods:
- Quantitative PCR measured CB1 receptor mRNA in liver tissue from 88 CHC patients, 12 controls, and 10 chronic hepatitis B (CHB) patients.
- The Huh7/JFH1 HCV cell culture model was utilized for result validation.
- CB1 expression was analyzed in relation to fibrosis stage, steatosis grade, and HCV genotype.
Main Results:
- CB1 was expressed in all CHC patients, with levels 6-fold higher than controls (P<0.001).
- CB1 expression increased with fibrosis stage and steatosis grade, particularly in genotype 3 CHC.
- HCV infection in cell culture induced an 8-fold increase in CB1, suggesting it is an HCV-inducible gene.
Conclusions:
- CB1 receptor is significantly upregulated in CHC patients.
- Increased CB1 expression is associated with steatosis in genotype 3 CHC.
- HCV infection directly induces CB1 expression, highlighting a potential therapeutic target.
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