Hepatic n-3/n-6 polyunsaturated fatty acid shift improves hepatic steatosis in farnesoid X receptor-null mice
Miyata, Masaaki | Kinoshita, Yuichi | Shinno, Kouhei | Sugiura, Yoshimasa | Harada, Kazuki
Mice lacking farnesoid X receptor (Fxr-null mice) are used as a model of non-alcoholic fatty liver disease because they exhibit higher levels of hepatic lipids and hepatic damage-associated diagnostic markers. The influence of hepatic accumulation of n-3 polyunsaturated fatty acid (PUFA) was investigated using Fxr-null mice fed either a corn oil (4 %) or fish oil (4 %) diet for 4 weeks. Hepatic accumulation of n-3 PUFA was observed in the fish-oil group. No significant differences in the activity of hepatic damage-associated diagnostic markers such as serum alanine aminotransferase were observed between the two groups. The levels of hepatic triglyceride, free fatty acid (FFA) and total cholesterol were significantly lower in the fish-oil group than in the corn-oil group. Marked decreases in lipid droplets were observed in the livers of mice in the fish-oil group. Only serum FFA levels were significantly lower in the fish-oil group than in the corn-oil group. Hepatic mRNA and protein levels of lipogenic enzymes, fatty acid synthase, and stearoyl CoA desaturase 1 were significantly lower in the fish-oil group than in the corn-oil group. These results suggest that hepatic n-3/n-6 PUFA shift improves hepatic steatosis by altering hepatic lipogenesis in Fxr-null mice.
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