Long-term feeding of a synthetic diet rich in disaccharides induces hepatic fibrosis in nonalcoholic fatty liver disease in Zucker rats

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease, and is commonly observed in patients with obesity or type 2 diabetes. The pathogenesis of hepatic fibrosis is clinically important to the outcome of NAFLD, however, is not well understood. Since dietary habits are often considered to be responsible for NAFLD, we used a synthetic diet rich in disaccharides (12.1% calorie sucrose and lactose), which can be considered for human consumption. We examined the long-term (24 weeks) effect of this diet on the liver of Zucker (fa/fa) rats. The synthetic diet-fed Zucker (fa/fa) rats showed hepatic fibrosis during the development of NAFLD with no apparent infiltration of inflammatory cells. They showed significantly elevated hepatic mRNA levels of proinflammatory and profibrogenic cytokines. These findings suggest that excess long-term feeding of a diet similar to the synthetic diet used in our Study leads to hepatic fibrosis during the development of NAFLD in patients with obesity or type 2 diabetes. Our results were different from NAFLD accompanied by infiltration of inflammatory cells. However, they also suggest that long-term feeding of this synthetic diet to Zucker (fa/fa) rats is useful for studying the hepatic fibrogenesis during the pathogenesis of NAFLD.