Abstract

To determine the effects of feeding soy or isoflavones on lipid homeostasis in early development, weanling rats were fed AIN-93G diets made with casein, soy protein isolate (SPI+), isoflavone-reduced SPI+ (SPI-), or casein supplemented with genistein or daidzein for 14 d. PPARalpha-regulated genes and proteins involved in fatty acid degradation were upregulated by SPI+ (P < 0.05) accompanied by increased promoter binding and expression of PPARalpha mRNA (P < 0.05). Feeding SPI- or pure isoflavones did not alter PPARalpha-regulated pathways. SPI+ feeding had similar effects on PPARgamma signaling. SPI+, SPI-, and casein plus isoflavones all increased liver X-receptor (LXR)alpha-regulated genes and enzymes involved in cholesterol homeostasis. Feeding SPI+ increased promoter binding of LXRalpha, expression of the transcription factor mRNA, and protein (P < 0.05). In a second experiment, male Sprague-Dawley rats were fed casein diets from postnatal d (PND) 24 to PND64 or were fed high-fat Western diets containing 5 g x kg(-1) cholesterol made with either casein or SPI+. Insulin resistance, steatosis, and hypercholesterolemia in the Western diet-fed rats were partially prevented by SPI+ (P < 0.05). Nuclear sterol receptor element binding protein (SREBP)-1c protein and mRNA and protein expression of enzymes involved in fatty acid synthesis were increased by feeding Western diets containing casein but not SPI+ (P < 0.05). These data suggest that activation of PPAR and LXR signaling and inhibition of SREBP-1c signaling may contribute to insulin sensitization and improved lipid homeostasis in SPI+-fed rats after consumption of diets high in fat and cholesterol.