期刊
TOXICOLOGICAL SCIENCES
卷 138, 期 1, 页码 161-174出版社
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kft331
关键词
adipogenesis; body composition; genistein; methylation; obesity; soy infant formula
类别
资金
- National Institute of Environmental Health Sciences (NIEHS) [T32 ES007326]
- College of ACES pilot grant
- National Center for Complementary and Alternative Medicines [P50AT006268]
- Office of Dietary Supplements
- National Cancer Institute
Genistein (Gen), the primary isoflavone in soy, has been shown to adversely affect various endocrine-mediated endpoints in rodents and humans. Soy formula intake by human infants has been associated with early age at menarche and decreased female-typical behavior in girls. Adipose deposition and expansion are also hormonally regulated and Gen has been shown to alter these processes. However, little is known about the impact of early-life soy intake on metabolic homeostasis in adulthood. The current study examined the impact of early-life Gen exposure on adulthood body composition (by magnetic resonance imaging) and the molecular signals mediating adipose expansion. From postnatal day (PND) 1 to 22, rat pups were daily orally dosed with 50mg/kg Gen to mimic blood Gen levels in human infants fed soy formula. Female but not male Gen-exposed rats had increased fat/lean mass ratio, fat mass, adipocyte size and number, and decreased muscle fiber perimeter. PND22 Gen-exposed females, but not males, had increased expression of adipogenic factors, including CCAAT/enhancer binding protein alpha (Cebp), CCAAT/enhancer binding protein beta (Cebp), and peroxisome proliferator-activated receptor gamma (Ppar). Furthermore, Wingless-related MMTV integration site 10b (Wnt10b), a critical regulator of adipogenic cell fate determination, was hypermethylated and had decreased expression in adipose of PND22 Gen-exposed females. These data suggest that developmental Gen exposure in rats has gender-specific effects on adiposity that closely parallel the effects of a postweaning high-fat diet and underscore the importance of considering timing of exposure and gender when establishing safety recommendations for early-life dietary Gen intake.
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