title: Genistein exposure during the early postnatal period favors the development of obesity in female, but not male rats.
abstract: 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 (Cebpα), CCAAT/enhancer binding protein beta (Cebpβ), and peroxisome proliferator-activated receptor gamma (Pparγ). 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.
authors.affiliation: * Department of Food Science and Human Nutrition;
authors.forename: Rita S
authors.initials: RS
authors.lastname: Strakovsky
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lezmi
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Flaws
authors.forename: Susan L
authors.initials: SL
authors.lastname: Schantz
authors.forename: Yuan-Xiang
authors.initials: YX
authors.lastname: Pan
authors.forename: William G
authors.initials: WG
authors.lastname: Helferich
mesh_terms: D050154:Adiposity / Q000187:drug effects*; D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001823:Body Composition; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000096:biosynthesis; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis; D005260:Female; D019833:Genistein / Q000633:toxicity*; D008297:Male; D009765:Obesity / Q000139:chemically induced* / Q000378:metabolism; D048789:Phytoestrogens / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D051153:Wnt Proteins / Q000096:biosynthesis
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; C545014:Cebpb protein, rat; D048789:Phytoestrogens; D051153:Wnt Proteins; C501228:Wnt10b protein, rat; D019833:Genistein
keywords: adipogenesis; body composition; genistein; methylation; obesity; soy infant formula.