Steatohepatitis is developed by a diet high in fat, sucrose, and cholesterol without increasing iron concentration in rat liver.

Abstract

Iron overload to the liver is known to be a pathogenesis of nonalcoholic steatohepatitis through oxidative stress. High-fat diets have been reported to increase iron concentration in livers that developed steatohepatitis in experimental animals. However, the effect of high-fat diets on hepatic iron concentration is controversial. We hypothesized that a diet high in lard, cholesterol, and sucrose (Western diet) leads to the development of steatohepatitis without increasing hepatic iron concentration. Rats were given either a control or the Western diet for 12 weeks. The Western diet increased triacylglycerol concentration and oxidative stress markers such as the concentration of thiobarbituric acid reactive substances and messenger RNA (mRNA) expression of heme oxygenase-1 in the liver. The Western diet also increased the mRNA expression of macrophage-1 antigen, cluster of differentiation (CD) 45, and CD68 in the liver, and nuclear factor κB level in liver nuclear fraction, suggesting the development of hepatic inflammation. Histological observation also indicated fatty liver and hepatic inflammation in the rats given the Western diet. In contrast, the Western diet decreased iron concentration in the liver. These results clearly indicated that the diet high in lard, cholesterol, and sucrose induces steatohepatitis without increasing hepatic iron concentration.