Abstract
Background: Understanding the pathogenesis of nonalcoholic steatohepatitis (NASH) in humans has been hampered by the
lack of a comprehensive and physiological small animal model of NASH. We previously reported a dietary (high-fat and high-cholesterol; HFC diet) -induced NASH model that developed advanced fibrosis within a relatively short period (9 weeks) using
Sprague-Dawley (SD) rats (age, 9 weeks).
Methods: In this study, we evaluated the age-related alterations of NASH in 9-, 18-, and 27-week-old male SD rats that were
fed an HFC diet (30% fat, 1.25% cholesterol, and 0.5% sodium cholate, w/w) for 9 weeks (six rats/group).
Results: Age-dependent increases in serum transaminases, insulin, and insulin resistance index were observed with or
without a significant difference after the 9-week rearing period. Histopathological findings such as hepatic steatosis, lobular
inflammation, and hepatocyte ballooning were similar regardless of age, but hepatic fibrosis was more evident in the older
groups. Rats in all three groups developed NASH at a high rate (83.3% or higher in each group). The mRNA levels of fibrosis-related genes encoding transforming growth factor-β (TGF-β) and α-smooth muscle actin (α-SMA) in the liver were low in the
youngest group and high in the older groups, although this difference was not statistically significant.
Conclusion: These results and those from our previous study indicate that a 9-week HFC diet-induced NASH model using
SD rats can be applied a relatively wide range of ages (5-27 weeks of old), and that the risk of NASH-related fibrosis increases
with age.
