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We investigated the effects of dietary fat energy restriction and fish oil intake on glucose and lipid metabolism in female KK mice with high-fat (HF) diet-induced obesity. Mice were fed a lard/safflower oil (LSO50) diet consisting of 50 energy% (en%) lard/safflower oil as the fat source for 12 weeks. Then, the mice were fed various fat energy restriction (25 en% fat) diets - LSO, FO2.5, FO12.5 or FO25 - containing 0, 2.5, 12.5, or 25 en% fish oil, respectively, for 9 weeks. Conversion from a HF diet to each fat energy restriction diet significantly decreased final body weights and visceral and subcutaneous fat mass in all fat energy restriction groups, regardless of fish oil contents. Hepatic triglyceride and cholesterol levels markedly decreased in the FO12.5 and FO25 groups, but not in the LSO group. Although plasma insulin levels did not differ among groups, the blood glucose areas under the curve in the oral glucose tolerance test were significantly lower in the FO12.5 and FO25 groups. Real-time polymerase chain reaction analysis showed fatty acid synthase mRNA levels significantly decreased in the FO25 group, and stearoyl-CoA desaturase 1 mRNA levels markedly decreased in the FO12.5 and FO25 groups. These results demonstrate that body weight gains were suppressed by dietary fat energy restriction even in KK mice with HF diet-induced obesity. We also suggested that the combination of fat energy restriction and fish oil feeding decreased fat droplets and ameliorated hepatic hypertrophy and insulin resistance with suppression of de novo lipogenesis in these mice., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Although cholesterol plays various important roles in the body, when overconsumed, it causes atherosclerosis and results in ischemic heart disease. On the other hand, dietary fish oils contain n-3 fatty acids, such as eicosapentaenoic acid and docosahexaenoic acid, which prevent ischemic heart disease. This effect of n-3 fatty acids mainly results from the combined effects of inhibiting lipogenesis via a decrease of the mature form of sterol regulatory element-binding proteins (SREBPs) and stimulating fatty acid oxidation via peroxisome proliferator-activator receptor (PPAR) alpha activation in the liver. In this study, we examined the interactive effects on lipid metabolism of dietary 2% cholesterol (w/w) and 20% or 50% energy fish oil. In a safflower oil diet with 2% cholesterol, hepatic lipids accumulated. On the other hand, hepatic lipids did not accumulate in the fish oil diets with cholesterol. Furthermore, in the groups with fish oil energy ratios of 20%, the negative feedback control of cholesterol affected SREBP-2, and the actions of fish oil and cholesterol were equivalent, but this was not observed in the cases with fish oil energy ratios of 50%. The results of this study suggest that differences in lipid accumulation in the body are due to differences in lipid source and energy ratios which differentially impact the control of transcription factors by cholesterol., ((c) 2010 Elsevier Inc. All rights reserved.)