A novel hamster nonalcoholic steatohepatitis model induced by a high-fat and high-cholesterol diet

Nonalcoholic steatohepatitis (NASH), in which there is steatosis and fibrosis in the liver, is linked to metabolic syndrome and progresses to hepatic cirrhosis. In this study, a novel hamster NASH model derived from metabolic syndrome was made using hamsters. Hamsters were fed a normal or a high-fat and high-cholesterol (HFC) diet for 12 weeks. Body weight and the ratio of liver weight to body weight were significantly greater in HFC diet-fed hamsters than in normal diet-fed hamsters. Triglyceride, low-density lipoprotein cholesterol, and glucose levels in blood were significantly increased in HFC diet-fed hamsters, and blood pressure also tended to be high, suggesting that the HFC diet-fed hamsters developed metabolic syndrome. Hepatic steatosis and fibrosis were observed in liver sections of HFC diet-fed hamsters, as in patients with NASH, but they were not seen in normal diet-fed hamsters. Chymase generates angiotensin II and transforming growth factor (TGF)-beta, both of which are related to hepatic steatosis and fibrosis, and a significant augmentation of chymase activity was observed in livers from HFC diet-fed hamsters. Both angiotensin II and TGF-beta were also significantly increased in livers of HFC diet-fed hamsters. Thus, HFC diet-fed hamsters might develop metabolic syndrome-derived NASH that clinically resembles that in NASH patients.