Cholesterol-fed rabbit as a unique model of nonalcoholic, nonobese, non-insulin-resistant fatty liver disease with characteristic fibrosis.
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.
Kainuma
Mosaburo
M
Department of Japanese Oriental Medicine, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, Japan.
Fujimoto
Makoto
M
Sekiya
Nobuyasu
N
Tsuneyama
Koichi
K
Cheng
Chunmei
C
Takano
Yasuo
Y
Terasawa
Katsutoshi
K
Shimada
Yutaka
Y
D000818:Animals; D002791:Cholesterol, Dietary / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D005234:Fatty Liver / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008054:Lipid Peroxides / Q000097:blood; D008055:Lipids / Q000097:blood; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000209:etiology* / Q000473:pathology; D008297:Male; D011817:Rabbits; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000097:blood
D002791:Cholesterol, Dietary; D007328:Insulin; D008054:Lipid Peroxides; D008055:Lipids; D016212:Transforming Growth Factor beta