Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver morbidity and mortality, and there is still no proven
effective therapy. The endocannabinoid system plays an important role in various liver diseases. Activin A is a member of the
transforming growth factor beta (TGF-) superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological
actions of activin A. This study was designed to investigate the effect of rimonabant (a potent cannabinoid receptor1 (CB1)
antagonist) on NAFLD induced with a choline-deficient (CD) diet in rats, as well as to detect whether it can alter the hepatic
expression of activin A and follistatin. Forty rats were distributed among 4 groups: the control group, the rimonabant treatment
group (normal rats that received rimonabant); the CD diet group (NAFLD induced with a CD diet); and the CD diet + rimonabant
group (NAFLD treated with rimonabant). It was found that the CD diet caused significant increase in liver index, serum levels of
liver enzymes, malondialdehyde (MDA), TGF-1, activin A, and CB1 expression in liver tissue, with a significant decrease in
glutathione peroxidase (GSH-Px) and follistatinmRNAexpression in liver tissues. The administration of rimonabant significantly
improved all of the studied parameters compared with the group fed the CD diet alone. Histopathological examination supported
these results. We concluded that rimonabant significantly counteracted NAFLD induced with the CD diet by decreasing
oxidative stress and hepatic expression of TGF-1, and modulating the hepatic expression of activin A and follistatin.
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