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Nutrition and Disease

Rats Fed Fructose-Enriched Diets Have Characteristics of Nonalcoholic Hepatic Steatosis^1–3,

⁴ Department of Internal Medicine, and ⁵ Department of Pathology, Teikyo University School of Medicine, Tokyo, 173-8605, Japan; ⁶ Department of Internal Medicine, Kawakita General Hospital, Tokyo, 166-8588, Japan; ⁷ Department of Applied Biological Chemistry, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka, 599-8531, Japan; and ⁸ Research and Development Center, Nagaoka Perfumery Company, Ibaraki, Osaka, 567-0005, Japan

Nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease are increasing in adults and are likely to be increasing in children. Both conditions are hepatic manifestations of metabolic syndrome. Experimental animals fed fructose-enriched diets are widely recognized as good models for metabolic syndrome. However, few reports have described the hepatic pathology of these experimental animals. In this study, 5-wk-old Wistar specific pathogen-free rats, which are a normal strain, were fed experimental diets for 5 wk. We then evaluated the degree of steatohepatitis. The 5 diet groups were as follows: cornstarch (70% wt:wt) [control (C)], high-fructose (70%) (HFr), high-sucrose (70%) (HS), high-fat (15%) (HF), and high-fat (15%) high-fructose (50%) (HFHFr) diets. The macrovesicular steatosis grade, liver:body weight ratio, and hepatic triglyceride concentration were significantly higher in the HFr group than in the other 4 groups. However, the HFr group had a significantly lower ratio of epididymal white fat:body weight than the other 4 groups and had a lower final body weight than the HF and HFHFr groups. The HF group had a greater final body weight than the C, HFr, and HS groups, but no macrovesicular steatosis was observed. The HFr group had a significantly higher grade of lobular inflammation than the other 4 groups. The distribution of lobular inflammation was predominant over portal inflammation, which is consistent with human NASH. In conclusion, rats fed fructose-enriched diets are a better model for NASH than rats fed fat-enriched diets.

^* To whom correspondence should be addressed. E-mail: t-kawa{at}med.teikyo-u.ac.jp.

Manuscript received 16 February 2009. Initial review completed 30 March 2009. Revision accepted 30 August 2009.

Published online 23 September 2009.