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Cholesterol-fed rabbit as a unique model of nonalcoholic, nonobese, non-insulin-resistant fatty liver disease with characteristic fibrosis

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Abstract

Background

The number of patients suffering from metabolic syndrome is increasing rapidly. Metabolic syndrome causes severe pathological changes in various organs, including the liver, and its main phenotype is nonalcoholic fatty liver disease (NAFLD). NAFLD has a broad spectrum ranging from simple fatty change to severe steatohepatitis with marked fibrosis. Recently, several experimental animal models for NAFLD have been proposed. However, most were established by rather artificial conditions such as genetic alteration. In the present study, we tried to establish a unique animal model mimicking some of the physiopathological features of NAFLD using high-cholesterol-fed rabbits.

Methods

Male rabbits fed with standard rabbit food containing 1% cholesterol for 8 weeks and 12 weeks were compared to controls (six rabbits/group). The weight of food was strictly restricted to 100 g/rabbit per day.

Results

Body weights and fasting plasma insulin levels showed no significant differences among the groups. In contrast, characteristic fine fibrosis was extended from perivenular to pericellular areas, and microvesicular fatty change with ballooning degeneration was observed in perivenular areas in livers of the cholesterol-fed rabbits. Increase of serum cholesterol level, activation of hepatic stellate cells, and exposure to oxidative stress were also recognized.

Conclusions

Cholesterol-fed rabbits share several physiopathological features of NAFLD. Because this model did not show insulin resistance or obesity, it may be useful for elucidating the mechanism of NAFLD related mainly to hyperlipidemia.

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Authors and Affiliations

  1. Department of Japanese Oriental Medicine, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

    Mosaburo Kainuma, Makoto Fujimoto & Yutaka Shimada

  2. First Department of Pathology, Faculty of Medicine, University of Toyama, Toyama, Japan

    Makoto Fujimoto, Koichi Tsuneyama & Yasuo Takano

  3. Department of Frontier Japanese Oriental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan

    Nobuyasu Sekiya

  4. 21st Century COE Program, University of Toyama, Toyama, Japan

    Koichi Tsuneyama, Katsutoshi Terasawa & Yutaka Shimada

  5. Allergy and Clinical Immunology, University of California, Davis, CA, USA

    Chunmei Cheng

  6. Department of Japanese Oriental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan

    Katsutoshi Terasawa

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  1. Mosaburo Kainuma
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  2. Makoto Fujimoto
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  3. Nobuyasu Sekiya
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  4. Koichi Tsuneyama
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  5. Chunmei Cheng
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  6. Yasuo Takano
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  7. Katsutoshi Terasawa
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Kainuma, M., Fujimoto, M., Sekiya, N. et al. Cholesterol-fed rabbit as a unique model of nonalcoholic, nonobese, non-insulin-resistant fatty liver disease with characteristic fibrosis. J Gastroenterol 41, 971–980 (2006). https://doi.org/10.1007/s00535-006-1883-1

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  • DOI: https://doi.org/10.1007/s00535-006-1883-1

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