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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.

DESIGN

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.

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  • Authors+Show Affiliations

    ,

    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).

    ,

    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).

    ,

    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).

    ,

    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).

    ,

    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).

    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).

    Source

    MeSH

    Adipose Tissue
    Adiposity
    Aged
    Cross-Over Studies
    Dietary Supplements
    Double-Blind Method
    Equol
    Female
    Gene Expression
    Genistein
    Humans
    Isoflavones
    Middle Aged
    Netherlands
    Nutritional Status
    Postmenopause
    Surveys and Questionnaires

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    25332325

    Citation

    van der Velpen, Vera, et al. "Isoflavone Supplement Composition and Equol Producer Status Affect Gene Expression in Adipose Tissue: a Double-blind, Randomized, Placebo-controlled Crossover Trial in Postmenopausal Women." The American Journal of Clinical Nutrition, vol. 100, no. 5, 2014, pp. 1269-77.
    van der Velpen V, Geelen A, Hollman PC, et al. Isoflavone supplement composition and equol producer status affect gene expression in adipose tissue: a double-blind, randomized, placebo-controlled crossover trial in postmenopausal women. Am J Clin Nutr. 2014;100(5):1269-77.
    van der Velpen, V., Geelen, A., Hollman, P. C., Schouten, E. G., van 't Veer, P., & Afman, L. A. (2014). Isoflavone supplement composition and equol producer status affect gene expression in adipose tissue: a double-blind, randomized, placebo-controlled crossover trial in postmenopausal women. The American Journal of Clinical Nutrition, 100(5), pp. 1269-77. doi:10.3945/ajcn.114.088484.
    van der Velpen V, et al. Isoflavone Supplement Composition and Equol Producer Status Affect Gene Expression in Adipose Tissue: a Double-blind, Randomized, Placebo-controlled Crossover Trial in Postmenopausal Women. Am J Clin Nutr. 2014;100(5):1269-77. PubMed PMID: 25332325.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Isoflavone supplement composition and equol producer status affect gene expression in adipose tissue: a double-blind, randomized, placebo-controlled crossover trial in postmenopausal women. AU - van der Velpen,Vera, AU - Geelen,Anouk, AU - Hollman,Peter C H, AU - Schouten,Evert G, AU - van 't Veer,Pieter, AU - Afman,Lydia A, Y1 - 2014/08/20/ PY - 2014/10/22/entrez PY - 2014/10/22/pubmed PY - 2015/2/24/medline SP - 1269 EP - 77 JF - The American journal of clinical nutrition JO - Am. J. Clin. Nutr. VL - 100 IS - 5 N2 - 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. DESIGN: 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. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/25332325/Isoflavone_supplement_composition_and_equol_producer_status_affect_gene_expression_in_adipose_tissue:_a_double_blind_randomized_placebo_controlled_crossover_trial_in_postmenopausal_women_ L2 - https://academic.oup.com/ajcn/article-lookup/doi/10.3945/ajcn.114.088484 DB - PRIME DP - Unbound Medicine ER -