The influence of fish oil-enriched Sasa-kamaboko (a Japanese processed seafood) diet on lipid metabolism was investigated using mice lacking farnesoid X receptor (FXR) as a fatty liver disease model. Sasa-kamaboko (SK) was made from Alaska pollock surimi (fish paste), enriched with fish oil (0%, 2.5%, or 5.0%) and then freeze-dried. Fxr-null mice were fed the dried SK, mixed with AIN-93M chow in the ratio 1:1 (50% SK diet) or 1:3 (25% SK diet), for 4 weeks. Hepatic triglyceride levels, and total cholesterol levels were significantly decreased, which were dependent on the amount of added fish oil in 25% and 50% SK diets. Hepatic fatty acid synthase (Fas), acetyl-CoA carboxylase 1 (Acc1), and stearoyl CoA desaturase 1 (Scd1) mRNA levels and Fas protein levels were decreased in groups fed fish oil-enriched 50% SK diets. Brain and serum non-esterified fatty acid levels were significantly decreased in the groups fed fish oil-enriched 50% SK diet, whereas brain and serum, (but not hepatic) phospholipid levels were significantly increased in the groups. Hepatic, serum and brain n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA; 22:6 n-3), and eicosapentaenoic acid (EPA; 20:5 n-3) levels (except for brain EPA levels) were significantly increased in groups fed fish oil-enriched 50% SK diet, whereas hepatic and serum mono-unsaturated fatty acid, oleic acid (18:1 n-9), and palmitoleic acid (16:1 n-7) levels were significantly decreased in the groups. These results suggest that a diet containing fish oil-enriched SK enhances hepatic lipid-lowering through the alteration of hepatic fatty acid composition in a fatty liver disease mouse model.