title: Soy and the soy isoflavone genistein promote adipose tissue development in male mice on a low-fat diet.
abstract: OBJECTIVE
  Several nutrients act as phytoestrogens, being anti-adipogenic when consumed with a fat-rich diet. Their effect on a low-fat diet (LFD) background is unknown. We tested soy and genistein effects on adipose tissue in LFD-fed mice and genistein activity in the 3T3-L1 adipogenesis model.
  
  
  METHODS
  C57BL/6 J male mice were fed an 8.5% soy-supplemented LFD (SS-LFD) or a soy-free LFD (SF-LFD) for 147 days. Groups of 3-week-old (pubertal) and 6-week-old (adult) mice on the SF-LFD were also treated with 17ß-estradiol (E2, 5 µg/kg/day) ip or pure genistein (5 mg/kg/day) by gavage for 15 days. Body fat deposition and gene expression profiles were evaluated. E2 and genistein effects on ERα, ERβ and PPARγ transcriptional activities were characterized in ERα- or ERβ-transfected 3T3L1 cells during differentiation, by the use of reporter plasmids.
  
  
  RESULTS
  The SS-LFD group increased fat mass compared with the SF-LFD group. Genistein alone increased while E2 decreased fat pads in the 15-day-treated mice. In visceral fat, genistein differentially regulated 13 metabolic pathways compared to E2. PPARγ-controlled genes were downregulated by E2, while they were upregulated by genistein. In 3T3-L1 cells, genistein activated ERβ-driven transcription, differentiation and lipid accumulation, while inhibited ERα-driven transcription, without effects on lipid accumulation. E2 activated both ERs only in preadipocytes. In differentiated untransfected cells, genistein inhibited PPARγ, while activated PPARγ in the presence of ERβ.
  
  
  CONCLUSIONS
  Soy and genistein at nutritional doses induce fat development in LFD-fed mice and adipogenesis in 3T3-L1 cells, with a mechanism that involves, at least in vitro, ERβ and is dependent on cell differentiation stage.
authors.affiliation: Biotechnology/3rd Laboratory and Department of Diagnostics, Civic Hospital of Brescia, 25123, Brescia, Italy.|Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Zanella
authors.affiliation: Biotechnology/3rd Laboratory and Department of Diagnostics, Civic Hospital of Brescia, 25123, Brescia, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Marrazzo
authors.affiliation: Biotechnology/3rd Laboratory and Department of Diagnostics, Civic Hospital of Brescia, 25123, Brescia, Italy.|Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Biasiotto
authors.affiliation: Biotechnology/3rd Laboratory and Department of Diagnostics, Civic Hospital of Brescia, 25123, Brescia, Italy.
authors.forename: Marialetizia
authors.initials: M
authors.lastname: Penza
authors.affiliation: Pharmaceutical Sciences Department, Università di Firenze, Florence, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Romani
authors.affiliation: Pharmaceutical Sciences Department, Università di Firenze, Florence, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Vignolini
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Caimi
authors.affiliation: Biotechnology/3rd Laboratory and Department of Diagnostics, Civic Hospital of Brescia, 25123, Brescia, Italy. diego.dilorenzo@yahoo.it.
authors.forename: Diego
authors.initials: D
authors.lastname: Di Lorenzo
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000187:drug effects; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D018752:Diet, Fat-Restricted; D015536:Down-Regulation; D004958:Estradiol / Q000008:administration & dosage; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D019833:Genistein / Q000008:administration & dosage* / Q000097:blood; D005951:Glucose Tolerance Test; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D013025:Glycine max / Q000737:chemistry*; D059467:Transcriptome
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D047495:PPAR gamma; D004958:Estradiol; D019833:Genistein
keywords: Adipocyte differentiation; Adipose deposition; Estrogen receptors; Phytoestrogens