van der Poorten, David, Shahidi, Mahsa, Tay, Enoch, Sesha, Jayshree, Tran, Kayla, McLeod, Duncan, Milliken, Jane S., Ho, Vikki, Hebbard, Lionel W., Douglas, Mark W., and George, Jacob (2010) Hepatitis C virus induces the cannabinoid receptor 1. PLoS ONE, 5 (9). e12841. pp. 1-10.

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Abstract

BACKGROUND

Activation of hepatic CB(1) receptors (CB(1)) is associated with steatosis and fibrosis in experimental forms of liver disease. However, CB(1) expression has not been assessed in patients with chronic hepatitis C (CHC), a disease associated with insulin resistance, steatosis and metabolic disturbance. We aimed to determine the importance and explore the associations of CB(1) expression in CHC.

METHODS

CB(1) receptor mRNA was measured by real time quantitative PCR on extracted liver tissue from 88 patients with CHC (genotypes 1 and 3), 12 controls and 10 patients with chronic hepatitis B (CHB). The Huh7/JFH1 Hepatitis C virus (HCV) cell culture model was used to validate results.

PRINCIPAL FINDINGS

CB(1) was expressed in all patients with CHC and levels were 6-fold higher than in controls (P<0.001). CB(1) expression increased with fibrosis stage, with cirrhotics having up to a 2 fold up-regulation compared to those with low fibrosis stage (p<0.05). Even in mild CHC with no steatosis (F0-1), CB(1) levels remained substantially greater than in controls (p<0.001) and in those with mild CHB (F0-1; p<0.001). Huh7 cells infected with JFH-1 HCV showed an 8-fold upregulation of CB(1), and CB(1) expression directly correlated with the percentage of cells infected over time, suggesting that CB(1) is an HCV inducible gene. While HCV structural proteins appear essential for CB(1) induction, there was no core genotype specific difference in CB(1) expression. CB(1) significantly increased with steatosis grade, primarily driven by patients with genotype 3 CHC. In genotype 3 patients, CB(1) correlated with SREBP-1c and its downstream target FASN (SREBP-1c; R=0.37, FASN; R=0.39, p<0.05 for both).

CONCLUSIONS/SIGNIFICANCE

CB(1) is up-regulated in CHC and is associated with increased steatosis in genotype 3. It is induced by the hepatitis C virus.

Item ID:	40174
Item Type:	Article (Research - C1)
ISSN:	1932-6203
Additional Information:	© 2010 van der Poorten et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funders:	Gastroenterological Society of Australia (GESA) , Australian National Health and Medical Research Council (NHMRC), CJ Martin Fellowship, Robert W. Storr Bequest to the University of Sydney
Projects and Grants:	NHMRC #402577, NHMRC #219282
Date Deposited:	31 Aug 2015 01:18
FoR Codes:	11 MEDICAL AND HEALTH SCIENCES > 1115 Pharmacology and Pharmaceutical Sciences > 111501 Basic Pharmacology @ 100%
SEO Codes:	92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920105 Digestive System Disorders @ 100%
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