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First published online September 12, 2008
Experimental Biology and Medicine 233:1242-1254 (2008)
doi: 10.3181/0802-RM-60
© 2008 by the Society for Experimental Biology and Medicine

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ORIGINAL RESEARCH ARTICLE

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

T. M. Badger*,{dagger},1, M. J. J. Ronis*,{ddagger}, G. Wolff*, S. Stanley*, M. Ferguson*, K. Shankar*,{ddagger}, P. Simpson§ and C.-H. Jo§

* Arkansas Children’s Nutrition Center, Little Rock, Arkansas 72202; and {dagger} Department of Physiology & Biophysics, {ddagger} Department of Pharmacology & Toxicology, and § Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72202

To whom requests for reprints should be addressed at 1 Arkansas Children’s Nutrition Center, Physiology & Biophysics, 1120 Marshall Street, N2001D, Slot 512–20B, Little Rock, AR 72202. E-mail: badgerthomasm{at}uams.edu

Agouti (Avy/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. Avy/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 Avy/a offspring had lower hepatosteatosis (P < 0.05) and increased (P < 0.05) expression of CYP4a 14, a PPAR{alpha}-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 PPAR{alpha} 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 PPAR{alpha}-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 Avy/a mice. These findings, when compared with those of previously published studies of Avy/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

Key Words: soy • epigenetics • steatosis • PPAR-alpha







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