Endocannabinoid receptor CB2 in nonalcoholic fatty liver disease.
OBJECTIVE
Fatty infiltration and fibrosis are major issues in chronic liver disease. Recent reports suggest a role for the endocannabinoid system in these processes.


OBJECTIVE
To characterize localization and expression of CB2 in normal liver and nonalcoholic fatty liver.


METHODS
We studied 64 liver biopsies: eight were considered normal; 56 had a diagnosis of nonalcoholic fatty liver disease (NAFLD); 32 with nonalcoholic steatosis and 24 nonalcoholic steatohepatitis (NASH). CB2 immunolocalization was studied in 38 samples in paraffin blocks using immunohistochemistry, and a computerized semiquantitative analysis was carried out. CB2 mRNA expression was assessed through RT-PCR in 26 frozen liver samples and the ratio CB2/beta-actin was used to evaluate differences between groups. Statistical analysis was performed with central tendency measures and the Mann-Whitney U-test. We considered as significant differences those with a P-value <0.05.


RESULTS
Neither parenchymal nor nonparenchymal cells in normal liver tissue react towards anti-CB2 antibodies. All the samples from patients with steatosis and nonalcoholic steatohepatitis showed hepatocellular immunoreactivity. Cholangiocytes were positive only in the NAFLD group. Normal liver tissue showed a normalized CB2/beta-actin ratio of 0.001+/-0.01, steatosis 6.52+/-17.3 (P=0.05 vs normal) and NASH 6.49+/-12.2 (P=0.06 vs normal and P=0.6 vs steatosis).


CONCLUSIONS
CB2 receptors are expressed by hepatocytes in nonalcoholic fatty liver disease but not in normal liver.
Mendez-Sanchez
N
N
Department of Biomedical Research, Gastroenterology & Liver Unit, Puente de Piedra 150, Col. Toriello Guerra, Mexico City, Mexico. nmendez@medicasur.org.mx
Zamora-Valdes
D
D
Pichardo-Bahena
R
R
Barredo-Prieto
B
B
Ponciano-Rodriguez
G
G
Bermejo-Martínez
L
L
Chavez-Tapia
N C
NC
Baptista-González
H A
HA
Uribe
M
M
D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D006505:Hepatitis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
D012333:RNA, Messenger; D043885:Receptor, Cannabinoid, CB2