Effects of soy isoflavones, genistein and daidzein, on the hepatic gene expression profile and indices for lipid metabolism were compared in rats. In the first experiment (Expt. 1), animals were fed diets containing 2 g/kg of either genistein or daidzein, or a control diet free of isoflavone for 14 days. In the second experiment (Expt. 2), rats were fed diets containing 1 or 2 g/kg of genistein, or an isoflavone-free diet for 16 days. Genistein at a dietary level of 2 g/kg reduced serum triacylglycerol concentrations in both experiments, and serum concentrations of cholesterol in Expt. 2. However, daidzein at 2 g/kg did not decrease serum lipid concentrations in Expt. 1. A DNA microarray analysis in Expt. 1 showed that genistein was stronger than daidzein in affecting gene expression in liver, targeting many genes involved in lipid and carbohydrate metabolism. Detailed analyses indicated that alterations in the expression of genes related to lipogenesis are primarily responsible for the serum lipid-lowering effect of genistein. This notion was supported by analyses of the activity of enzymes involved in lipogenesis in Expt. 2.
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