Spontaneous development of hepatocellular carcinomas in the FLS mice with hereditary fatty liver

Insulin Resistance, Steatohepatitis, and Hepatocellular Carcinoma in a New Congenic Strain of Fatty Liver Shionogi (FLS) Mice with the Lepob Gene

“…In addition to the lipid metabolism abnormalities in the liver and blood, steatohepatitis-like lesions including micro-abscesses and infiltration of mononuclear cells were observed in the liver of FLS mice. Interestingly, aged FLS mice frequently developed hepatic tumors including hepatocellular adenoma, carcinoma, and peliosis hepatis [31]. These findings suggest that the FLS mouse has potential as a model of steatohepatitis and hepato-carcinogenesis in human NASH.…”

“…The incidence of hepatic tumors in male FLS mice was 9% at 13-14 months of age [31]. The FLSLep ob /Lep ob mice also developed hepatic tumors, and their incidence was high compared with FLS mice at 12 months of age.…”

“…A preliminary genetic cross study suggested that the fatty liver formation in the FLS mice is caused by a complex polygenic trait. Interestingly, aged FLS mice frequently develop hepatocellular adenoma, carcinoma, and peliosis hepatis [31]. Therefore, the FLS mouse might be a useful animal model for human NASH.…”

Involvement of microsomal triglyceride transfer protein in nonalcoholic steatohepatitis in novel spontaneous mouse model

“…The inbred Fatty Liver Shionogi (FLS) mouse is reported to develop hepatic steatosis under normal chow as a polygenic trait [19], and hepatocellular adenomas and carcinomas at an older age [20], making their liver lesions comparable to NASH. In addition, we reported that the glucose tolerance of this mouse is impaired [17], suggesting that the FLS mouse could serve as a model for clarifying the biological link between NAFLD and diabetes.…”

Hepatocellular carcinoma and nonalcoholic steatohepatitis developing during long-term administration of valproic acid

“…However, the remaining cases of HCC, approximately 20%, can develop in a non-cirrhotic liver. There is a report of an animal study in which a new inbred mouse strain, fatty liver Shionogi, spontaneously developed fatty liver and HCC in the noncirrhotic liver [21]. Although it remains uncertain whether cirrhosis is required for the development of HCC, at least, this case indicates that HCC can arise in a non-cirrhotic NASH liver.…”