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Feeding diets containing soy protein isolate (SPI) at weaning results in activation of PPAR and LXR‐mediated pathways as a result of upregulation of transcription factor expression.

The current study examined the effects of feeding soy protein isolate (SPI) on expression of genes and transcription factors involved in fatty acid (FA) and cholesterol metabolism and transport in weanling rats. Sprague‐Dawley rats were weaned onto AIN‐93G diets containing SPI or casein (CAS) as the sole protein source from dams fed casein diets throughout gestation and lactation. At sacrifice on PND34, expression of PPAR alpha‐regulated genes (acyl CoA oxidase (ACO), hydroxyacyl‐Coenzyme A dehydrogenase, carnitine palmitoyltransferase); PPAR gamma‐regulated genes (glucokinase,, CD36) and LXR‐regulated genes (CYP7A1, ABCG5, ABCG8) were induced (p < 0.05) by feeding SPI relative to expression in liver of those rats fed CAS as determined by real time RT‐PCR. This was accompanied by increased binding of the PPARs and LXR to their response elements on the ACO, glucokinase and CYP7A1 promoters as measured in EMSA and ChIP assays. Increased expression of PPAR and LXR mRNA and apoprotein was also observed (p < 0.05) in SPI fed rats. In addition, rats fed high fat/high cholesterol diets and SPI via total enteral nutrition had reduced steatosis; hepatic FA and cholesterol content (p < 0.05) relative to those fed CAS. These data suggest that SPI increases hepatic FA and cholesterol metabolism and transport via induction of PPARs and LXR.