title: Soy protein isolate reduces hepatosteatosis in yellow Avy/a mice without altering coat color phenotype.
abstract: 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 A(vy)/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 PPARalpha-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 PPARalpha 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 PPARalpha-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.
authors.affiliation: Arkansas Children's Nutrition Center, Physiology & Biophysics, Little Rock, AR 72202, USA. badgerthomasm@uams.edu
authors.forename: T M
authors.initials: TM
authors.lastname: Badger
authors.forename: M J J
authors.initials: MJ
authors.lastname: Ronis
authors.forename: G
authors.initials: G
authors.lastname: Wolff
authors.forename: S
authors.initials: S
authors.lastname: Stanley
authors.forename: M
authors.initials: M
authors.lastname: Ferguson
authors.forename: K
authors.initials: K
authors.lastname: Shankar
authors.forename: P
authors.initials: P
authors.lastname: Simpson
authors.forename: C-H
authors.initials: CH
authors.lastname: Jo
mesh_terms: D054366:Agouti Signaling Protein / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy* / Q000517:prevention & control; D005260:Female; D019833:Genistein / Q000494:pharmacology; D006200:Hair Color / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D047493:PPAR alpha / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D030262:Soybean Proteins / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D054366:Agouti Signaling Protein; D005227:Fatty Acids; D047493:PPAR alpha; D030262:Soybean Proteins; C515183:a protein, mouse; D019833:Genistein