Abstract
Nonalcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome. In this study, we investigated histological and biochemical changes in NAFLD and the gene expression involving de novo lipogenesis in Otsuka Long-Evans Tokushima fatty (OLETF) rats. We used OLETF rats and Long-Evans Tokushima Otsuka (LETO) rats as animal models of NAFLD and as controls, respectively. Consistent observations were made at 4-week intervals up to 50 weeks of age, and all rats were fed ad libitum with standard food. Biochemical and histological changes were observed, and gene expression involved in de novo lipogenesis was measured using real-time polymerase chain reactions. As a results hepatic micro- and macrovesicular steatosis and hepatocyte ballooning were evident in the OLETF rats at 22–38 weeks of age but disappeared after 42 weeks; no fibrosis or collagen deposition was observed. Gene expression involved in de novo lipogenesis followed a pattern similar to that of the histological changes. In conclusion, in the absence of dietary manipulation, hepatic steatosis in OLETF rats is evident at 22–38 weeks and declines after 42 weeks. Therefore, OLETF rats at 22–38 weeks are recommended as animal models of hepatic steatosis.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is presently well recognized as a hepatic manifestation of metabolic syndrome [1]
Serum glucose and TG levels were higher in the Otsuka Long-Evans Tokushima fatty (OLETF) rats than in the Long-Evans Tokushima Otsuka (LETO) rats at all ages (Figures 1(b) and 1(c)), and total cholesterol (TC) levels were higher in the OLETF rats than in the LETO rats after 26 weeks (Figure 1(d))
At 50 weeks, levels of AST and free fatty acid were higher in the OLETF rats than in the LETO rats, but no significant differences were observed in insulin and ALT levels (Table 2)
Summary
Nonalcoholic fatty liver disease (NAFLD) is presently well recognized as a hepatic manifestation of metabolic syndrome [1]. NAFLD is strongly associated with obesity, type 2 diabetes mellitus, and hyperlipidemia [2]. The spectrum of NAFLD ranges from simple steatosis thorough nonalcoholic steatohepatitis (NASH) to cirrhosis [3]. 20%–30% of NAFLD patients progress to NASH and to cirrhosis [4]. NAFLD is estimated to affect up to 30% of all adults in the United States and up to 70% of obese individuals [5]. Day and James have proposed a two-hit hypothesis to explain the progression of NAFLD. The first hit involves the deposition of triglycerides in hepatocytes (hepatic steatosis) and the second hit refers to the cellular events leading to hepatic inflammation (NASH) [6]
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