title: Isoflavone supplement composition and equol producer status affect gene expression in adipose tissue: a double-blind, randomized, placebo-controlled crossover trial in postmenopausal women.
abstract: BACKGROUND
  Isoflavone supplements, consumed by women experiencing menopausal symptoms, are suggested to have positive effects on menopause-related adiposity and cardiovascular disease risk profile, but discussions about their safety are still ongoing.
  
  
  OBJECTIVE
  The objective was to study the effects of an 8-wk consumption of 2 different isoflavone supplements compared with placebo on whole-genome gene expression in the adipose tissue of postmenopausal women.
  
  
  METHODS
  This double-blind, randomized, placebo-controlled crossover intervention consisted of 2 substudies, one with a low-genistein (LG) supplement (56% daidzein + daidzin, 16% genistein + genistin, and 28% glycitein + glycitin) and the other with a high-genistein (HG) supplement (49% daidzein + daidzin, 41% genistein + genistin, and 10% glycitein + glycitin). Both supplements provided ∼ 100 mg isoflavones/d (aglycone equivalents). After the 8-wk isoflavone and placebo period, whole-genome arrays were performed in subcutaneous adipose tissue of postmenopausal women (n = 26 after LG, n = 31 after HG). Participants were randomized by equol-producing phenotype, and data analysis was performed per substudy for equol producers and nonproducers separately.
  
  
  RESULTS
  Gene set enrichment analysis showed downregulation of expression of energy metabolism-related genes after LG supplementation (n = 24) in both equol-producing phenotypes and oppositely regulated expression for equol producers (down) and nonproducers (up) after HG supplementation (n = 31). Expression of inflammation-related genes was upregulated in equol producers but downregulated in nonproducers, independent of supplement type. Only 4.4-7.0% of the genes with significantly changed expression were estrogen responsive. Body weight, adipocyte size, and plasma lipid profile were not affected by isoflavone supplementation.
  
  
  CONCLUSIONS
  Effects of isoflavones on adipose tissue gene expression were influenced by supplement composition and equol-producing phenotype, whereas estrogen-responsive effects were lacking. LG isoflavone supplementation resulted in a caloric restriction-like gene expression profile for both producer phenotypes and pointed toward a potential beneficial effect, whereas both supplements induced anti-inflammatory gene expression in equol producers. The study was registered at clinicaltrials.gov as NCT01556737.
authors.affiliation: From the Division of Human Nutrition, Wageningen University, Wageningen, Netherlands (VvdV, AG, PCHH, EGS, PvtV, and LAA), and Institute of Food Safety, Wageningen University & Research Centre, Wageningen, Netherlands (PCHH).
authors.forename: Vera
authors.initials: V
authors.lastname: van der Velpen
authors.affiliation: From the Division of Human Nutrition, Wageningen University, Wageningen, Netherlands (VvdV, AG, PCHH, EGS, PvtV, and LAA), and Institute of Food Safety, Wageningen University & Research Centre, Wageningen, Netherlands (PCHH).
authors.forename: Anouk
authors.initials: A
authors.lastname: Geelen
authors.affiliation: From the Division of Human Nutrition, Wageningen University, Wageningen, Netherlands (VvdV, AG, PCHH, EGS, PvtV, and LAA), and Institute of Food Safety, Wageningen University & Research Centre, Wageningen, Netherlands (PCHH).
authors.forename: Peter C H
authors.initials: PC
authors.lastname: Hollman
authors.affiliation: From the Division of Human Nutrition, Wageningen University, Wageningen, Netherlands (VvdV, AG, PCHH, EGS, PvtV, and LAA), and Institute of Food Safety, Wageningen University & Research Centre, Wageningen, Netherlands (PCHH).
authors.forename: Evert G
authors.initials: EG
authors.lastname: Schouten
authors.affiliation: From the Division of Human Nutrition, Wageningen University, Wageningen, Netherlands (VvdV, AG, PCHH, EGS, PvtV, and LAA), and Institute of Food Safety, Wageningen University & Research Centre, Wageningen, Netherlands (PCHH).
authors.forename: Pieter
authors.initials: P
authors.lastname: van 't Veer
authors.affiliation: From the Division of Human Nutrition, Wageningen University, Wageningen, Netherlands (VvdV, AG, PCHH, EGS, PvtV, and LAA), and Institute of Food Safety, Wageningen University & Research Centre, Wageningen, Netherlands (PCHH).
authors.forename: Lydia A
authors.initials: LA
authors.lastname: Afman
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects; D000368:Aged; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D060754:Equol / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D019833:Genistein / Q000008:administration & dosage; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage*; D008875:Middle Aged; D009426:Netherlands; D009752:Nutritional Status; D017698:Postmenopause; D011795:Surveys and Questionnaires
chemical_list: D007529:Isoflavones; C040641:genistin; C013908:daidzin; D060754:Equol; C004742:daidzein; C086566:glycitein; D019833:Genistein; C433283:glycitin