Horm Metab Res 2017; 49(06): 457-465
DOI: 10.1055/s-0043-108250
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Dietary Isoflavone-Dependent and Estradiol Replacement Effects on Body Weight in the Ovariectomized (OVX) Rat

Ashley L. Russell*
1   Program in Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
,
Jamie Moran Grimes*
1   Program in Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
2   Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
,
Danette F. Cruthirds
1   Program in Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
,
Joanna Westerfield
2   Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
,
Lawren Wooten
2   Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
,
Margaret Keil
3   NIH – NICHD, Bethesda, MD, USA
,
Michael J. Weiser
4   DSM Nutritional Products Inc., Human Nutrition & Health, Boulder, CO, USA
,
Michael R. Landauer
5   Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
,
Robert J. Handa
6   Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, USA
,
T. John Wu
1   Program in Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
2   Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
,
Darwin O. Larco
2   Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
› Author Affiliations
Further Information

Publication History

received 07 September 2016

accepted 28 March 2017

Publication Date:
08 May 2017 (online)

Abstract

17β-Estradiol is known to regulate energy metabolism and body weight. Ovariectomy results in body weight gain while estradiol administration results in a reversal of weight gain. Isoflavones, found in rodent chow, can mimic estrogenic effects making it crucial to understand the role of these compounds on metabolic regulation. The goal of this study is to examine the effect of dietary isoflavones on body weight regulation in the ovariectomized rat. This study will examine how dietary isoflavones can interact with estradiol treatment to affect body weight. Consistent with previous findings, animals fed an isoflavone-rich diet had decreased body weight (p<0.05), abdominal fat (p<0.05), and serum leptin levels (p<0.05) compared to animals fed an isoflavone-free diet. Estradiol replacement resulted in decreased body weight (p<0.05), abdominal fat (p<0.05), and serum leptin (p<0.05). Current literature suggests the involvement of cytokines in the inflammatory response of body weight gain. We screened a host of cytokines and chemokines that may be altered by dietary isoflavones or estradiol replacement. Serum cytokine analysis revealed significant (p<0.05) diet-dependent increases in inflammatory cytokines (keratinocyte-derived chemokine). The isoflavone-free diet in OVX rats resulted in the regulation of the following cytokines and chemokines: interleukin-10, interleukin-18, serum regulated on activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 (p<0.05). Overall, these results reveal that estradiol treatment can have differential effects on energy metabolism and body weight regulation depending on the presence of isoflavones in rodent chow.

* These authors contributed equally to this work


 
  • References

  • 1 Hoegh-Andersen P, Tanko LB, Andersen TL, Lundberg CV, Mo JA, Heegaard AM, Delaisse JM, Christgau S. Ovariectomized rats as a model of postmenopausal osteoarthritis: Validation and application. Arthr Res Ther 2004; 6: R169-R180
  • 2 Larco DO, Cruthirds DF, Weiser MJ, Handa RJ, Wu TJ. The effect of chronic immobilization stress on leptin signaling in the ovariectomized (OVX) rat. Endocrine 2012; 42: 717-725
  • 3 Nelson LR, Bulun SE. Estrogen production and action. J Am Acad Dermatol 2001; 45 3 Suppl S116-S124
  • 4 Dechering K, Boersma C, Mosselman S. Estrogen receptors alpha and beta: two receptors of a kind?. Curr Med Chem 2000; 7: 561-576
  • 5 Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A 1996; 93: 5925-5930
  • 6 Mosselman S, Polman J, Dijkema R. ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett 1996; 392: 49-53
  • 7 Toran-Allerand CD, Singh M, Setalo Jr. G. Novel mechanisms of estrogen action in the brain: New players in an old story. Front Neuroendocrinol 1999; 20: 97-121
  • 8 Wegorzewska IN, Walters K, Weiser MJ, Cruthirds DF, Ewell E, Larco DO, Handa RJ, Wu TJ. Postovariectomy weight gain in female rats is reversed by estrogen receptor alpha agonist, propylpyrazoletriol. Am J Obstetr Gynecol 2008; 199 (67) e1-e5
  • 9 Ohlsson C, Hellberg N, Parini P, Vidal O, Bohlooly YM, Rudling M, Lindberg MK, Warner M, Angelin B, Gustafsson JA. Obesity and disturbed lipoprotein profile in estrogen receptor-alpha-deficient male mice. Biochem Biophys Res Commun 2000; 278: 640-645
  • 10 Cooke PS, Heine PA, Taylor JA, Lubahn DB. The role of estrogen and estrogen receptor-alpha in male adipose tissue. Mol Cell Endocrinol 2001; 178: 147-154
  • 11 Wisse BE. The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol 2004; 15: 2792-2800
  • 12 Benoit SC, Clegg DJ, Seeley RJ, Woods SC. Insulin and leptin as adiposity signals. Rec Prog Horm Res 2004; 59: 267-285
  • 13 Gao Q, Mezei G, Nie Y, Rao Y, Choi CS, Bechmann I, Leranth C, Toran-Allerand D, Priest CA, Roberts JL, Gao XB, Mobbs C, Shulman GI, Diano S, Horvath TL. Anorectic estrogen mimics leptin’s effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Nat Med 2007; 13: 89-94
  • 14 Trayhurn P, Beattie JH. Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc 2001; 60: 329-339
  • 15 King MW. Adipose tissue: Not just fat. http://themedicalbiochemistrypage.org/adipose-tissue.php
  • 16 Fain JN. Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam Horm 2006; 74: 443-477
  • 17 Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Aller Clin Immunol 2005; 115: 911-919 quiz 20
  • 18 Neels JG, Badeanlou L, Hester KD, Samad F. Keratinocyte-derived chemokine in obesity: expression, regulation, and role in adipose macrophage infiltration and glucose homeostasis. J Biol Chem 2009; 284: 20692-20698
  • 19 Nehete P, Magden ER, Nehete B, Hanley PW, Abee CR. Obesity related alterations in plasma cytokines and metabolic hormones in chimpanzees. Int J Inflam 2014; 856749
  • 20 Troseid M, Seljeflot I, Arnesen H. The role of interleukin-18 in the metabolic syndrome. Cardiovasc Diabetol 2010; 9: 11
  • 21 Purohit A, Newman SP, Reed MJ. The role of cytokines in regulating estrogen synthesis: Implications for the etiology of breast cancer. Breast Cancer Res 2002; 4: 65-69
  • 22 Shivers KY, Amador N, Abrams L, Hunter D, Jenab S, Quinones-Jenab V. Estrogen alters baseline and inflammatory-induced cytokine levels independent from hypothalamic-pituitary-adrenal axis activity. Cytokine 2015; 72: 121-129
  • 23 Esposito E, Iacono A, Raso GM, Pacilio M, Coppola A, Di Carlo R, Meli R. Raloxifene, a selective estrogen receptor modulator, reduces carrageenan-induced acute inflammation in normal and ovariectomized rats. Endocrinology 2005; 146: 3301-3308
  • 24 Cuzzocrea S, Santagati S, Sautebin L, Mazzon E, Calabro G, Serraino I, Caputi AP, Maggi A. 17beta-estradiol antiinflammatory activity in carrageenan-induced pleurisy. Endocrinology 2000; 141: 1455-1463
  • 25 Masiukiewicz US, Mitnick M, Grey AB, Insogna KL. Estrogen modulates parathyroid hormone-induced interleukin-6 production in vivo and in vitro. Endocrinology 2000; 141: 2526-2531
  • 26 Liu H, Liu K, Bodenner DL. Estrogen receptor inhibits interleukin-6 gene expression by disruption of nuclear factor kappaB transactivation. Cytokine 2005; 31: 251-257
  • 27 Pervin S, Singh R, Rosenfeld ME, Navab M, Chaudhuri G, Nathan L. Estradiol suppresses MCP-1 expression In vivo: Implications for atherosclerosis. Arterioscler Thromb Vasc Biol 1998; 18: 1575-1582
  • 28 Miyazaki K. Novel approach for evaluation of estrogenic and anti-estrogenic activities of genistein and daidzein using B16 melanoma cells and dendricity assay. Pigm Cell Res 2004; 17: 407-412
  • 29 Bedell S, Nachtigall M, Naftolin F. The pros and cons of plant estrogens for menopause. J Steroid Biochem Mol Biol 2014; 139: 225-236
  • 30 Morito K, Hirose T, Kinjo J, Hirakawa T, Okawa M, Nohara T, Ogawa S, Inoue S, Muramatsu M, Masamune Y. Interaction of phytoestrogens with estrogen receptors alpha and beta. Biol Pharm Bull 2001; 24: 351-356
  • 31 Patisaul HB, Jefferson W. The pros and cons of phytoestrogens. Front Neuroendocrinol 2010; 31: 400-419
  • 32 Jefferson WN, Padilla-Banks E, Newbold RR. Adverse effects on female development and reproduction in CD-1 mice following neonatal exposure to the phytoestrogen genistein at environmentally relevant doses. Biol Reprod 2005; 73: 798-806
  • 33 Lephart ED, Setchell KD, Handa RJ, Lund TD. Behavioral effects of endocrine-disrupting substances: phytoestrogens. ILAR J 2004; 45: 443-454
  • 34 Bu L, Setchell KD, Lephart ED. Influences of dietary soy isoflavones on metabolism but not nociception and stress hormone responses in ovariectomized female rats. Reprod Biol Endocrinol 2005; 3: 58
  • 35 Lund TD, Lephart ED. Dietary soy phytoestrogens produce anxiolytic effects in the elevated plus-maze. Brain Res 2001; 913: 180-184
  • 36 Reeves PG, Nielsen FH, Fahey Jr. GC. AIN-93 purified diets for laboratory rodents: Final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 1993; 123: 1939-1951
  • 37 Teklad Global 18 % Protein Rodent Diet [Internet]. ENVIGO. 2015;
  • 38 Franke AA, Custer LJ, Cerna CM, Narala K. Rapid HPLC analysis of dietary phytoestrogens from legumes and from human urine. Proc Soc Exp Biol Med 1995; 208: 18-26
  • 39 Hartley DE, Edwards JE, Spiller CE, Alom N, Tucci S, Seth P, Forsling ML, File SE. The soya isoflavone content of rat diet can increase anxiety and stress hormone release in the male rat. Psychopharmacology 2003; 167: 46-53
  • 40 Cruthirds DF, Siangco AL, Hartman CJ, Sandefur DC, Spencer Jr. JM, Dyer CA, Larco DO, Wu TJ. Effects of immobilization stress and hormonal treatment on nociception. AANA J 2011; 79: 375-380
  • 41 McGinnis MY, Krey LC, MacLusky NJ, McEwen BS. Steroid receptor levels in intact and ovariectomized estrogen-treated rats: an examination of quantitative, temporal and endocrine factors influencing the efficacy of an estradiol stimulus. Neuroendocrinology 1981; 33: 158-165
  • 42 Weigt C, Hertrampf T, Zoth N, Fritzemeier KH, Diel P. Impact of estradiol, ER subtype specific agonists and genistein on energy homeostasis in a rat model of nutrition induced obesity. Mol Cell Endocrinol 2012; 351: 227-238
  • 43 Coppack SW. Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc 2001; 60: 349-356
  • 44 Szkudelska K, Nogowski L, Szkudelski T. Genistein affects lipogenesis and lipolysis in isolated rat adipocytes. J Steroid Biochem Mol Biol 2000; 75: 265-271
  • 45 Yang H, Li F, Xiong X, Kong X, Zhang B, Yuan X, Fan J, Duan Y, Geng M, Li L, Yin Y. Soy isoflavones modulate adipokines and myokines to regulate lipid metabolism in adipose tissue, skeletal muscle and liver of male Huanjiang mini-pigs. Mol Cell Endocrinol 2013; 365: 44-51
  • 46 Kim HK, Nelson-Dooley C, Della-Fera MA, Yang JY, Zhang W, Duan J, Hartzell DL, Hamrick MW, Baile CA. Genistein decreases food intake, body weight, and fat pad weight and causes adipose tissue apoptosis in ovariectomized female mice. J Nutr 2006; 136: 409-414
  • 47 Naaz A, Yellayi S, Zakroczymski MA, Bunick D, Doerge DR, Lubahn DB, Helferich WG, Cooke PS. The soy isoflavone genistein decreases adipose deposition in mice. Endocrinology 2003; 144: 3315-3320
  • 48 Jungbauer A, Medjakovic S. Phytoestrogens and the metabolic syndrome. J Steroid Biochem Mol Biol 2014; 139: 277-289
  • 49 Schwartz MW, Peskind E, Raskind M, Boyko EJ, Porte Jr. D. Cerebrospinal fluid leptin levels: Relationship to plasma levels and to adiposity in humans. Nat Med 1996; 2: 589-593
  • 50 Baskin DG, Figlewicz Lattemann D, Seeley RJ, Woods SC, Porte Jr. D, Schwartz MW. Insulin and leptin: Dual adiposity signals to the brain for the regulation of food intake and body weight. Brain Res 1999; 848: 114-123
  • 51 Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, Friedman JM. Abnormal splicing of the leptin receptor in diabetic mice. Nature 1996; 379: 632-635
  • 52 Ladyman SR, Grattan DR. JAK-STAT and feeding. JAKSAT 2013; 2: e23675
  • 53 Diano S, Kalra SP, Sakamoto H, Horvath TL. Leptin receptors in estrogen receptor-containing neurons of the female rat hypothalamus. Brain Res 1998; 812: 256-259
  • 54 Festa A, D’Agostino Jr. R, Howard G, Mykkanen L, Tracy RP, Haffner SM. Chronic subclinical inflammation as part of the insulin resistance syndrome: The Insulin Resistance Atherosclersis Study (IRAS). Circulation 2000; 102: 42-47
  • 55 Wallenius V, Wallenius K, Ahren B, Rudling M, Carlsten H, Dickson SL, Ohlsson C, Jansson JO. Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 2002; 8: 75-79
  • 56 Tsigos C, Kyrou I, Chala E, Tsapogas P, Stavridis JC, Raptis SA, Katsilambros N. Circulating tumor necrosis factor alpha concentrations are higher in abdominal versus peripheral obesity. Metab Clin Exp 1999; 48: 1332-1335
  • 57 Chavey C, Lazennec G, Lagarrigue S, Clape C, Iankova I, Teyssier J, Annicotte JS, Schmidt J, Mataki C, Yamamoto H, Sanches R, Guma A, Stich V, Vitkova M, Jardin-Watelet B, Renard E, Strieter R, Tuthill A, Hotamisligil GS, Vidal-Puig A, Zorzano A, Langin D, Fajas L. CXC ligand 5 is an adipose-tissue derived factor that links obesity to insulin resistance. Cell Metab 2009; 9: 339-349
  • 58 Czlonkowska A, Ciesielska A, Gromadzka G, Kurkowska-Jastrzebska I. Estrogen and cytokines production – the possible cause of gender differences in neurological diseases. Curr Pharm Design 2005; 11: 1017-1030
  • 59 Rogers A, Eastell R. The effect of 17beta-estradiol on production of cytokines in cultures of peripheral blood. Bone 2001; 29: 30-34
  • 60 Brown CM, Mulcahey TA, Filipek NC, Wise PM. Production of proinflammatory cytokines and chemokines during neuroinflammation: novel roles for estrogen receptors alpha and beta. Endocrinology 2010; 151: 4916-4925
  • 61 Patisaul HB, Dindo M, Whitten PL, Young LJ. Soy isoflavone supplements antagonize reproductive behavior and estrogen receptor alpha- and beta-dependent gene expression in the brain. Endocrinology 2001; 142: 2946-2952