Soy Protein Isolate Reduces Hepatosteatosis in Yellow Avy/a Mice Without Altering Coat Color Phenotype

Agouti ( A vy/ a) mice fed an AIN-93G diet containing the soy isoflavone genistein (GEN) prior to and during pregnancy were reported to shift coat color and body composition phenotypes from obese-yellow towards lean pseudoagouti, suggesting epigenetic programming. Human consumption of purified GEN is rare and soy protein is the primary source of GEN. Virgin a/a female and Avy/a male mice were fed AIN-93G diets made with casein (CAS) or soy protein isolate (SPI) (the same approximate GEN levels as in the above mentioned study) for 2 wks prior to mating. A vy /a offspring were weaned to the same diets and studied at age 75 d. Coat color distribution did not differ among diets, but SPI-fed, obese A vy/ a offspring had lower hepatosteatosis ( P < 0.05) and increased ( P < 0.05) expression of CYP4a 14, a PPARα-regulated gene compared to CAS controls. Similarly, weanling male Sprague-Dawley (SD) rats fed SPI had elevated hepatic Acyl Co-A Oxidase (ACO) mRNA levels and increased in vitro binding of PPARα to the PPRE promoter response element. In another hepatosteatosis model, adult SD rats fed a high fat/cholesterol diet, SPI reduced ( P < 0.05) steatosis. Thus, 1) consumption of diets made with SPI partially protected against hepatosteatosis in yellow mice and in SD rats, and this may involve induction of PPARα-regulated genes; and 2) the lifetime ( in utero, neonatal and adult) exposure to dietary soy protein did not result in a shift in coat color phenotype of A vy/ a mice. These findings, when compared with those of previously published studies of A vy/ a mice, lead us to conclude that: 1) the effects of purified GEN differ from those of SPI when GEN equivalents are closely matched; 2) SPI does not epigenetically regulate the agouti locus to shift the coat color phenotype in the same fashion as GEN alone; and 3) SPI may be beneficial in management of non-alcoholic fatty liver disease