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Title: In Utero exposure to soy protein isolate does not produce epigenetic changes in heterozygous viable yellow agouti (Avy/a) mice offspring, but does alter body composition and prevents hepatosteatosis

Author
item BADGER, THOMAS - ACNC/UAMS
item WOLFF, GEORGE - NCTR/ACNC CONTRACT
item STANLEY, STEVE - ACNC/UAMS
item FERGUSON, MATTHEW - ACNC/ACH
item RONIS, MARTIN - ACNC/UAMS

Submitted to: Endocrinology
Publication Type: Proceedings
Publication Acceptance Date: 2/15/2007
Publication Date: 6/2/2007
Citation: Badger, T.M., Wolff, G., Stanley, S., Ferguson, M., Ronis, M.J. 2007. In utero exposure to soy protein isolate does not produce epigenetic changes in heterozygous viable yellow agouti (Avy/a) mice offspring, but does alter body composition and prevents hepatosteatosis. The Endocrine Society, 89th Annual Meeting, June 2-5, 2007, Toronto, Canada. 2007 CDROM, Program No. OR16-4.

Interpretive Summary: Our Center has been studying the effects of soy infant formula on developing children. We have found that consumption of soy may improve body composition in children and rodents. Recently, a group from Duke University published results suggesting that genistein, a phytochemical in soy, reduced obesity in a genetically modified mouse, called the Agouti mouse. Since these investigators fed the mice purified genistein rather than feeding them soy protein, we replicated their experiment using a diet made with soy protein isolate rather than pure genistein. We did not find the dramatic results previously reported, but we did find some interesting results that are directly relevant to children. First, there was a lower body fat content in female mice fed soy and a dramatic reduction in steatosis, a liver disorder than is becoming much more prevalent in American children as the obesity epidemic continues to strike children at an ever younger age. These results suggest that soy foods may help improve body composition. In addition, it is clear that purified genistein does not have the same effects on developing animals as soy protein that contains the same amount of genistein.

Technical Abstract: Millions of pregnant women, fetuses and neonates have been exposed to soy foods containing phytoestrogen isoflavones such as genistein and daidzein for generations in Asia and for decades in the USA. Despite this long history, there are concerns about potential adverse developmental effects of soy feeding and disorders that might not become apparent until later in life. In a recently published study, virgin a/a female mice were mated with Avy/a males. This is a model of epigenetic imprinting resulting in genetically identical offspring of differing phenotypes either pseudoagouti (brown and lean) or obese yellow dependent on methylation status of the Agouti gene promoter. Avy/a offspring that were fed AIN-93G diets supplemented with genistein (GEN) had a coat color distribution shift from yellow toward pseudoagouti associated with hypermethylation at CG sites on the Agouti gene promoter; and decreased adult obesity. We essentially duplicated this latter study in our lab, except throughout the study (starting from before mating) mice were fed AIN-93G diets made with 100% protein as either casein (CAS) or soy protein isolate (SPI) rather than CAS supplemented with purified GEN. The coat color distribution did not differ between groups. However, yellow female Avy/a offspring had lower fat pad mass and reduced hepatosteatosis was observed in obese yellow offspring of both sexes (P<0.05). Thus, the in utero effects on the fetal epigenome and resultant shift in phenotype reported for feeding purified GEN does not occur when 100% of dietary protein is composed of SPI, demonstrating that dietary purified GEN effects differ from effects of SPI containing equivalent amounts of this phytoestrogen. However, soy protein intake appears to be involved in energy metabolism and lipid storage. Although the mechanisms are as yet unknown, these data suggest that SPI may be beneficial in management of heposteatosis.