Effects of dietary equol on body weight gain, intra-abdominal fat accumulation, plasma lipids, and glucose tolerance in ovariectomized Sprague-Dawley rats

Objective:To evaluate the effects of dietary equol, a metabolite of the phytoestrogen daidzein, on body weight gain, intra-abdominal fat accumulation, plasma leptin, lipids, and glucose tolerance in ovariectomized rats and to compare them to the effects of 17&bgr;-estradiol. Design:Twenty-eight female Sprague-Dawley rats were ovariectomized and fed soy-free chow with the addition of estradiol-3 benzoate (E2B) (10 mg/kg, n = 10) or equol (400 mg/kg, n = 10). The control group (n = 8) received soy-free chow only. Weight and food intake were recorded once weekly. After 6 weeks, intra-abdominal fat was measured using computed tomography, and the intraperitoneal glucose tolerance test was performed. In the seventh week, the animals were killed, blood was collected for plasma, and uteri were removed. Results:Dietary equol significantly increased uterine mass. This effect was, however, 3.5 times lower in magnitude compared to E2B. Similar to E2B, dietary equol decreased weight gain, intra-abdominal fat accumulation, and plasma leptin levels. Equol-treated animals had also lower plasma total cholesterol and triglyceride levels compared to controls. E2B treatment also decreased plasma total cholesterol as well as high-density lipoprotein and low-density lipoprotein cholesterol. In the glucose tolerance test, the area under the curve was significantly smaller in the E2B- and equol-treated animals compared to controls. Also, E2B-treated animals had lower fasting plasma insulin levels. Conclusions:In ovariectomized rats, dietary equol administration attenuates weight gain and shows favorable metabolic effects. However, because of its mild uterotrophic activity, its use in the prevention of postmenopausal weight gain and related metabolic disorders in women with an intact uterus is questionable in terms of safety and warrants further studies.

[1]  D. Rachoń,et al.  Effects of dietary equol on the pituitary of the ovariectomized rats. , 2007, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[2]  Evan R. Simpson,et al.  Of mice and men: the evolving phenotype of aromatase deficiency , 2006, Trends in Endocrinology & Metabolism.

[3]  M. Hamrick,et al.  Genistein decreases food intake, body weight, and fat pad weight and causes adipose tissue apoptosis in ovariectomized female mice. , 2006, The Journal of nutrition.

[4]  U. P. S. T. Force Hormone therapy for the prevention of chronic conditions in postmenopausal women: recommendations from the U.S. Preventive Services Task Force. , 2005 .

[5]  U. P. S. T. Force,et al.  Hormone Therapy for the Prevention of Chronic Conditions in Postmenopausal Women: Recommendations from the U.S. Preventive Services Task Force , 2005, Annals of Internal Medicine.

[6]  A. Arıcı,et al.  Phyto-oestrogens and the endometrium , 2004, The Lancet.

[7]  J. Katzenellenbogen,et al.  Estrogenicity of the Isoflavone Metabolite Equol on Reproductive and Non-Reproductive Organs in Mice1 , 2004, Biology of reproduction.

[8]  V. Unfer,et al.  Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study. , 2004, Fertility and sterility.

[9]  P. Bandosz,et al.  Knowledge and use of hormone replacement therapy among Polish women: estimates from a nationally representative study--HORTPOL 2002. , 2004, Maturitas.

[10]  M. Stefanick,et al.  Recommendations for estrogen and progestogen use in peri-and postmenopausal women: October 2004 position statement of The North American Menopause Society. , 2004, Menopause.

[11]  D. Kritz-Silverstein,et al.  Usual dietary isoflavone intake and body composition in postmenopausal women , 2003, Menopause.

[12]  Mary Cushman,et al.  Estrogen plus progestin and the risk of coronary heart disease. , 2003, The New England journal of medicine.

[13]  W. Banz,et al.  Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells. , 2003, The Journal of nutrition.

[14]  K. Setchell,et al.  Bioavailability, disposition, and dose-response effects of soy isoflavones when consumed by healthy women at physiologically typical dietary intakes. , 2003, The Journal of nutrition.

[15]  E. Vittinghoff,et al.  Glycemic Effects of Postmenopausal Hormone Therapy: The Heart and Estrogen/progestin Replacement Study: A Randomized, Double-Blind, Placebo-Controlled Trial , 2003, Annals of Internal Medicine.

[16]  H. Jarry,et al.  Phytoestrogens for hormone replacement therapy? , 2002, The Journal of Steroid Biochemistry and Molecular Biology.

[17]  K. Setchell,et al.  The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones. , 2002, The Journal of nutrition.

[18]  J. Sorkin,et al.  Comparison of VO2max and disease risk factors between perimenopausal and postmenopausal women , 2002, Menopause.

[19]  M. Rendell,et al.  Effects of Estrogen Replacement Therapy on Abdominal Fat Compartments as Related to Glucose and Lipid Metabolism in Early Postmenopausal Women , 2002, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[20]  J. Ashby,et al.  Critical Review and Evaluation of the Uterotrophic Bioassay for the Identification of Possible Estrogen Agonists and Antagonists: In Support of the Validation of the OECD Uterotrophic Protocols for the Laboratory Rodent , 2002, Critical reviews in toxicology.

[21]  B. Nicklas,et al.  Hormone replacement therapy, insulin sensitivity, and abdominal obesity in postmenopausal women. , 2002, Diabetes care.

[22]  S. B. Pedersen,et al.  Regulation of UCP1, UCP2, and UCP3 mRNA expression in brown adipose tissue, white adipose tissue, and skeletal muscle in rats by estrogen. , 2001, Biochemical and biophysical research communications.

[23]  G. Iwamoto,et al.  Increased adipose tissue in male and female estrogen receptor-α knockout mice , 2000 .

[24]  T. Sellers,et al.  Associations of general and abdominal obesity with multiple health outcomes in older women: the Iowa Women's Health Study. , 2000, Archives of internal medicine.

[25]  I. Godsland,et al.  Effects of oral and transdermal 17beta-estradiol with cyclical oral norethindrone acetate on insulin sensitivity, secretion, and elimination in postmenopausal women. , 2000, Metabolism: clinical and experimental.

[26]  M. J. Toth,et al.  Effect of menopausal status on insulin-stimulated glucose disposal: comparison of middle-aged premenopausal and early postmenopausal women. , 2000, Diabetes care.

[27]  E. Poehlman,et al.  Menopause‐Related Changes in Body Fat Distribution , 2000, Annals of the New York Academy of Sciences.

[28]  A. Abdel‐Rahman,et al.  Effect of long-term ovariectomy and estrogen replacement on the expression of estrogen receptor gene in female rats. , 2000, European journal of endocrinology.

[29]  H. Adlercreutz,et al.  Interindividual Variation in Metabolism of Soy Isoflavones and Lignans: Influence of Habitual Diet on Equol Production by the Gut Microflora , 2000, Nutrition and cancer.

[30]  J. Callés-Escandon,et al.  Relation of regional fat distribution to insulin sensitivity in postmenopausal women. , 2000, Fertility and Sterility.

[31]  A. Lethaby,et al.  Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding. , 2004, The Cochrane database of systematic reviews.

[32]  I Persson,et al.  Risk of endometrial cancer following estrogen replacement with and without progestins. , 1999, Journal of the National Cancer Institute.

[33]  J. Corton,et al.  Interaction of Estrogenic Chemicals and Phytoestrogens with Estrogen Receptor β. , 1998, Endocrinology.

[34]  E. Poehlman,et al.  Effects of the menopause transition on body fatness and body fat distribution. , 1998, Obesity research.

[35]  Organisation for Economic Cooperation and Development,et al.  Organisation for economic cooperation and development , 1998 .

[36]  N. Hoggard,et al.  Hormonal and neuroendocrine regulation of energy balance--the role of leptin. , 1998, Archiv fur Tierernahrung.

[37]  J. Callés-Escandon,et al.  Menopause, central body fatness, and insulin resistance: effects of hormone‐replacement therapy , 1998, Coronary artery disease.

[38]  M. K. James,et al.  Effect of postmenopausal hormone therapy on body weight and waist and hip girths. Postmenopausal Estrogen-Progestin Interventions Study Investigators. , 1997, The Journal of clinical endocrinology and metabolism.

[39]  J Ashby,et al.  The rodent uterotrophic assay: critical protocol features, studies with nonyl phenols, and comparison with a yeast estrogenicity assay. , 1997, Regulatory toxicology and pharmacology : RTP.

[40]  C. Darimont,et al.  Influence of Estrogenic Status on the Lipolytic Activity of Parametrial Adipose Tissue in Vivo: an in Situ Microdialysis Study. , 1997, Endocrinology.

[41]  H. Genant,et al.  The comparative effect on bone density, endometrium, and lipids of continuous hormones as replacement therapy (CHART study). A randomized controlled trial. , 1996, JAMA.

[42]  E. Poehlman,et al.  Changes in Energy Balance and Body Composition at Menopause: A Controlled Longitudinal Study , 1995, Annals of Internal Medicine.

[43]  P. Amouyel,et al.  Multiple coronary heart disease risk factors are associated with menopause and influenced by substitutive hormonal therapy in a cohort of French women. , 1995, Atherosclerosis.

[44]  R. Miksicek Interaction of naturally occurring nonsteroidal estrogens with expressed recombinant human estrogen receptor , 1994, The Journal of Steroid Biochemistry and Molecular Biology.

[45]  T. Buchanan,et al.  Original ArticlesComparison of Estimates of Insulin Sensitivity in Pre- and Postmenopausal Women Using the Insulin Tolerance Test and the Frequently Sampled Intravenous Glucose Tolerance Test , 1994 .

[46]  T. Buchanan,et al.  Comparison of estimates of insulin sensitivity in pre- and postmenopausal women using the insulin tolerance test and the frequently sampled intravenous glucose tolerance test. , 1994, Journal of the Society for Gynecologic Investigation.

[47]  J. Auwerx,et al.  Effects of sex steroids on hepatic and lipoprotein lipase activity and mRNA in the rat. , 1993, Hormone research.

[48]  M. Zamboni,et al.  Body fat distribution in pre- and post-menopausal women: metabolic and anthropometric variables and their inter-relationships. , 1992, International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity.

[49]  F. Vocci,et al.  Extrapolation of animal toxicity data to man. , 1988, Regulatory toxicology and pharmacology : RTP.

[50]  I W Davidson,et al.  Biological basis for extrapolation across mammalian species. , 1986, Regulatory toxicology and pharmacology : RTP.

[51]  P. Southwell-keely,et al.  The oestrogenicity of equol in sheep. , 1984, The Journal of endocrinology.

[52]  M. Greenwood,et al.  Effect of Estrogen on Lipoprotein Lipase Activity and Cytoplasmic Progestin Binding Sites in Lean and Obese Zucker Rats , 1984, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[53]  G. Wade,et al.  Food intake, body weight, and adiposity in female rats: actions and interactions of progestins and antiestrogens. , 1981, The American journal of physiology.

[54]  Y. Chao,et al.  Determinants of hepatic uptake of triglyceride-rich lipoproteins and their remnants in the rat. , 1980, The Journal of biological chemistry.

[55]  E. Roy,et al.  Role of estrogens in androgen-induced spontaneous activity in male rats. , 1975, Journal of comparative and physiological psychology.

[56]  M. Hamosh,et al.  The effect of estrogen on the lipoprotein lipase activity of rat adipose tissue. , 1975, The Journal of clinical investigation.

[57]  C. P. Richter,et al.  Comparison of the effects of gonadectomy of spontaneous activity of wild and domesticated Norway rats. , 1954, Endocrinology.

[58]  G. Haslewood,et al.  Equol, a new inactive phenol isolated from the ketohydroxyoestrin fraction of mares' urine. , 1932, Biochemical Journal.