Prevention and regression of non-alcoholic steatohepatitis (NASH) in a rat model by metabosartan, telmisartan

Abstract

The favorable metabolic effects of telmisartan have been attributed to its angiotensin II receptor blockade and action as a partial agonist of peroxisome proliferator-activated receptor (PPAR)-γ. We previously reported that administration of telmisartan markedly inhibited lipid accumulation in the liver in mice fed a high-fat diet. In the present study, we further examined the protective effect of telmisartan in a non-alcoholic steatohepatitis (NASH) model induced by feeding Wistar rats an L-methionine- and choline-deficient (MCA) diet. In the first experiment, rats were fed an MCA diet for 8 weeks with or without telmisartan (3 mg/kg/day). Liver fibrosis was observed by Masson trichrome staining, and co-treatment was shown to attenuate liver fibrosis. In the second experiment, Wistar rats were fed an MCA diet for 20 weeks, and telmisartan (3 mg/kg/day) was administered during weeks 0-20 as a preventive model or weeks 8-20 as a therapeutic model. As a result, telmisartan administration in both models significantly attenuated liver fibrosis and an increase in serum AST. Of importance, the HGF concentration in the liver was significantly increased in the telmisartan-treated group. Overall, telmisartan showed a potential action to improve NASH induced by an MCA diet, possibly due to increased HGF production through partial agonist of PPAR-γ. These favorable characteristics of telmisartan as a partial agonist of PPAR-γ may provide a benefit in the treatment of metabolic syndrome beyond its blood pressure-lowering effect.