Metabolic diseases including
nonalcoholic steatohepatitis develop due to various environmental factors. In particular, the westernization of food is closely related to the development of these diseases. In this study, we investigated pathophysiological changes in the livers of Zucker fatty (ZF) rats induced by feeding Western diets. Male ZF rats were fed a
sucrose/fat/
cholesterol-enriched diet (Western diet, WD) or standard diet (SD) for 18 weeks, from 7 to 25 weeks of age.
Body weight, food intake, and biochemical parameters were periodically measured, histopathological analyses were performed at 25 weeks, and
mRNA expression in the liver was determined. ZF rats fed the WD (ZF-WD rats) developed
obesity,
hyperinsulinemia,
hyperglycemia, and
hyperlipidemia, and their
alanine aminotransferase and
aspartate aminotransferase levels increased compared with those of ZF rats fed the SD (ZF-SD rats). Hepatic lesions including
fibrosis and
necrosis were observed in the ZF-WD rats at 25 weeks; however,
fibrosis and
necrosis were not observed in the ZF-SD rats. Oxidative stress markers also increased in the livers of ZF-WD rats. Hepatic
mRNA expression related to
inflammation and
fibrosis increased in the ZF-WD rats; however,
mRNA expression related to
lipid synthesis decreased.
Microsomal triglyceride transfer protein mRNA levels in the ZF-WD rats also decreased. In Zucker lean rats fed the WD, similar changes were observed in the liver; however, the hepatic changes were not serious compared with ZF-WD rats. In conclusion, hepatic lesions, such as
inflammation,
fibrosis, and
necrosis, were observed in the ZF-WD rats. The
sucrose/fat/
cholesterol-enriched diet induced significant lipotoxicity in the livers of animals in this
insulin-resistant model.