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Oestrogens, adipose tissues and environmental exposures influence obesity and diabetes across the lifecycle
Published online by Cambridge University Press: 02 February 2024
Abstract
Endogenous oestrogens regulate essential functions to include menstrual cycles, energy balance, adipose tissue distribution, pancreatic β-cell function, insulin sensitivity and lipid homeostasis. Oestrogens are a family of hormones which include oestradiol (E2), oestrone (E1) and oestriol (E3). Oestrogens function by binding and activating oestrogen receptors (ERs). Phytoestrogens are plant-derived compounds which exhibit oestrogenic-like activity and can bind to ERs. Phytoestrogens exert potential oestrogenic-like benefits; however, their effects are context-dependent and require cautious consideration regarding generalised health benefits. Xenoestrogens are synthetic compounds which have been determined to disrupt endocrine function through binding to ERs. Xenoestrogens enter the body through various routes and given their chemical structure they can accumulate, posing long-term health risks. Xenoestrogens interfere with endogenous oestrogens and their functions contributing to conditions like cancer, infertility, and metabolic disorders. Understanding the interplay between endogenous and exogenous oestrogens is critical in order to determine their potential health consequences and requires further investigation. This manuscript provides a summary of the role endogenous oestrogens have in regulating metabolic functions. Additionally, we discuss the impact phytoestrogens and synthetic xenoestrogens have on biological systems across various life stages. We highlight their mechanisms of action, potential benefits, risks and discuss the need for further research to bridge gaps in understanding and mitigate exposure-related health risks.
- Type
- Conference on ‘Understanding the Role of Sex and Gender in Nutrition Research’
- Information
- Copyright
- © Texas Tech University Health Science Center El Paso, 2024. Published by Cambridge University Press on behalf of The Nutrition Society
References
Reed, BG & Carr, BR (2018) The Normal Menstrual Cycle and the Control of Ovulation. Endotext. South Dartmouth, MA: MDText.com, Inc.Google Scholar
Mauvais-Jarvis, F, Clegg, DJ & Hevener, AL (2013) The role of estrogens in control of energy balance and glucose homeostasis. Endocr Rev 34, 309–338. doi: 10.1210/er.2012-1055.CrossRefGoogle ScholarPubMed
Bracht, JR, Vieira-Potter, VJ, De Souza Santos, R et al. (2020) The role of estrogens in the adipose tissue milieu. Ann N Y Acad Sci 1461, 127–143. doi: 10.1111/nyas.14281.CrossRefGoogle ScholarPubMed
Kuryłowicz, A (2023) Estrogens in adipose tissue physiology and obesity-related dysfunction. Biomedicines 11, 690. doi: 10.3390/biomedicines11030690.CrossRefGoogle ScholarPubMed
Mauvais-Jarvis, F (2016) Role of sex steroids in β cell function, growth, and survival. Trends Endocrinol Metab 27, 844–855. doi: 10.1016/j.tem.2016.08.008.CrossRefGoogle ScholarPubMed
Yan, H, Yang, W, Zhou, F et al. (2019) Estrogen improves insulin sensitivity and suppresses gluconeogenesis via the transcription factor foxo1. Diabetes 68, 291–304. doi: 10.2337/db18-0638.CrossRefGoogle ScholarPubMed
Palmisano, BT, Zhu, L & Stafford, JM (2017) Role of estrogens in the regulation of liver lipid metabolism. Adv Exp Med Biol 1043, 227–256. doi: 10.1007/978-3-319-70178-3_12
CrossRefGoogle ScholarPubMed
Bolego, C, Cignarella, A, Staels, B et al. (2013) Macrophage function and polarization in cardiovascular disease: a role of estrogen signaling? Arterioscler Thromb Vasc Biol 33, 1127–1134. doi: 10.1161/ATVBAHA.113.301328.CrossRefGoogle ScholarPubMed
Lizcano, F & Guzmán, G (2014) Estrogen deficiency and the origin of obesity during menopause. Biomed Res Int 2014, 757461. doi: 10.1155/2014/757461.CrossRefGoogle ScholarPubMed
Meng, Q, Li, J, Chao, Y et al. (2020)
β-estradiol adjusts intestinal function via ERβ and GPR30 mediated PI3K/AKT signaling activation to alleviate postmenopausal dyslipidemia. Biochem Pharmacol 180, 114134. doi: 10.1016/j.bcp.2020.114134.CrossRefGoogle ScholarPubMed
Liu, S & Mauvais-Jarvis, F (2010) Minireview: estrogenic protection of beta-cell failure in metabolic diseases. Endocrinology 151, 859–864. doi: 10.1210/en.2009-1107. (published correction appears in Endocrinology. 2010; 151, 4597).CrossRefGoogle Scholar
Santos, RS, Batista, TM, Camargo, RL et al. (2016) Lacking of estradiol reduces insulin exocytosis from pancreatic β-cells and increases hepatic insulin degradation. Steroids 114, 16–24. doi: 10.1016/j.steroids.2016.05.002.CrossRefGoogle ScholarPubMed
Della Torre, S (2020) Non-alcoholic fatty liver disease as a canonical example of metabolic inflammatory-based liver disease showing a sex-specific prevalence: relevance of estrogen signaling. Front Endocrinol (Lausanne) 11, 572490. doi: 10.3389/fendo.2020.572490.CrossRefGoogle ScholarPubMed
De Paoli, M, Zakharia, A & Werstuck, GH (2021) The role of estrogen in insulin resistance: a review of clinical and preclinical data. Am J Pathol 191, 1490–1498. doi: 10.1016/j.ajpath.2021.05.011.CrossRefGoogle ScholarPubMed
Straub, RH (2007) The complex role of estrogens in inflammation. Endocr Rev 28, 521–574. doi: 10.1210/er.2007-0001.CrossRefGoogle ScholarPubMed
Cui, J, Shen, Y & Li, R (2013) Estrogen synthesis and signaling pathways during aging: from periphery to brain. Trends Mol Med 19, 197–209. doi: 10.1016/j.molmed.2012.12.007.CrossRefGoogle ScholarPubMed
Jones, ME, Thorburn, AW, Britt, KL et al. (2000) Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity. Proc Natl Acad Sci U S A 97, 12735–12740. doi: 10.1073/pnas.97.23.12735.CrossRefGoogle ScholarPubMed
Dalla, C, Antoniou, K, Papadopoulou-Daifoti, Z et al. (2004) Oestrogen-deficient female aromatase knockout (ArKO) mice exhibit depressive-like symptomatology. Eur J Neurosci 20, 217–228. doi: 10.1111/j.1460-9568.2004.03443.x.CrossRefGoogle ScholarPubMed
Barakat, R, Oakley, O, Kim, H et al. (2016) Extra-gonadal sites of estrogen biosynthesis and function. BMB Rep 49, 488–496. doi: 10.5483/bmbrep.2016.49.9.141.CrossRefGoogle ScholarPubMed
Hilborn, E, Stål, O & Jansson, A (2017) Estrogen and androgen-converting enzymes 17β-hydroxysteroid dehydrogenase and their involvement in cancer: with a special focus on 17β-hydroxysteroid dehydrogenase type 1, 2, and breast cancer. Oncotarget 8, 30552–30562. doi: 10.18632/oncotarget.15547.CrossRefGoogle Scholar
Frick, KM (2009) Estrogens and age-related memory decline in rodents: what have we learned and where do we go from here? Horm Behav 55, 2–23. doi: 10.1016/j.yhbeh.2008.08.015.CrossRefGoogle Scholar
Zenclussen, ML, Casalis, PA, Jensen, F et al. (2014) Hormonal fluctuations during the estrous cycle modulate heme oxygenase-1 expression in the uterus. Front Endocrinol (Lausanne) 5, 32. doi: 10.3389/fendo.2014.00032.CrossRefGoogle ScholarPubMed
Caligioni, CS (2009) Assessing reproductive status/stages in mice. Curr Protoc Neurosci Appendix 4, Appendix-4I. doi: 10.1002/0471142301.nsa04is48.CrossRefGoogle Scholar
Wall, eg Desai, R, Khant Aung, Z et al. (2023) Unexpected plasma gonadal steroid and prolactin levels across the mouse estrous cycle. Endocrinology 164, bqad070. doi: 10.1210/endocr/bqad070.CrossRefGoogle ScholarPubMed
Park, YW, Zhu, S, Palaniappan, L, Heshka, S et al. (2003) The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988–1994. Arch Intern Med 163, 427–436. doi: 10.1001/archinte.163.4.427
CrossRefGoogle ScholarPubMed
Fabre, A, Tramunt, B, Montagner, A et al. (2023) Membrane estrogen receptor-α contributes to female protection against high-fat diet-induced metabolic disorders. Front Endocrinol (Lausanne) 14, 1215947. doi: 10.3389/fendo.2023.1215947
CrossRefGoogle ScholarPubMed
Wang, X, Ha, D, Yoshitake, R et al. (2021) Exploring the biological activity and mechanism of xenoestrogens and phytoestrogens in cancers: emerging methods and concepts. Int J Mol Sci 22, 8798. doi: 10.3390/ijms22168798.CrossRefGoogle ScholarPubMed
Domínguez-López, I, Yago-Aragón, M, Salas-Huetos, A et al. (2020) Effects of dietary phytoestrogens on hormones throughout a human lifespan: a review. Nutrients 12, 2456. doi: 10.3390/nu12082456.CrossRefGoogle ScholarPubMed
Desmawati, D & Sulastri, D (2019) Phytoestrogens and their health effect. Open Access Maced J Med Sci 7, 495–499. doi: 10.3889/oamjms.2019.044.CrossRefGoogle ScholarPubMed
Viggiani, MT, Polimeno, L, Di Leo, A et al. (2019) Phytoestrogens: dietary intake, bioavailability, and protective mechanisms against colorectal neoproliferative lesions. Nutrients 11, 1709. doi: 10.3390/nu11081709.CrossRefGoogle ScholarPubMed
Minutolo, F, Macchia, M, Katzenellenbogen, BS et al. (2011) Estrogen receptor β ligands: recent advances and biomedical applications. Med Res Rev 31, 364–442. doi: 10.1002/med.20186.CrossRefGoogle ScholarPubMed
Paterni, I, Granchi, C, Katzenellenbogen, JA et al. (2014) Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential. Steroids 90, 13–29. doi: 10.1016/j.steroids.2014.06.012.CrossRefGoogle ScholarPubMed
Patisaul, HB & Jefferson, W (2010) The pros and cons of phytoestrogens. Front Neuroendocrinol 31, 400–419. doi: 10.1016/j.yfrne.2010.03.003.CrossRefGoogle ScholarPubMed
Patisaul, HB (2017) Endocrine disruption by dietary phyto-oestrogens: impact on dimorphic sexual systems and behaviours. Proc Nutr Soc 76, 130–144. doi: 10.1017/S0029665116000677.CrossRefGoogle ScholarPubMed
Crisp, TM, Clegg, ED, Cooper, RL et al. (1998) Environmental endocrine disruption: an effects assessment and analysis. Environ Health Perspect 106, 11–56. doi: 10.1289/ehp.98106s111.CrossRefGoogle Scholar
Sonnenschein, C & Soto, AM (1998) An updated review of environmental estrogen and androgen mimics and antagonists. J Steroid Biochem Mol Biol 65, 143–150. doi: 10.1016/s0960-0760(98)00027-2.CrossRefGoogle Scholar
Mueller, G & Kim, UH (1978) Displacement of estradiol from estrogen receptors by simple alkyl phenols. Endocrinol 102, 1429–1435.CrossRefGoogle ScholarPubMed
McLachlan, JA (1993) Functional toxicology: a new approach to detect biologically active xenobiotics. Environ Health Perspect 101, 386–387. doi: 10.1289/ehp.93101386.CrossRefGoogle ScholarPubMed
Soto, AM, Chung, KL & Sonnenschein, C (1994) The pesticides endosulfan, toxaphene, and dieldrin have estrogenic effects on human estrogen-sensitive cells. Environ Health Perspect 102, 380–383. doi: 10.1289/ehp.94102380.CrossRefGoogle ScholarPubMed
Diamanti-Kandarakis, E, Bourguignon, JP, Giudice, LC et al. (2009) Endocrine-disrupting chemicals: an endocrine society scientific statement. Endocr Rev 30, 293–342. doi: 10.1210/er.2009-0002.CrossRefGoogle ScholarPubMed
Zoeller, RT, Brown, TR, Doan, LL et al. (2012) Endocrine-disrupting chemicals and public health protection: a statement of principles from The Endocrine Society. Endocrinology 153, 4097–4110. doi: 10.1210/en.2012-1422.CrossRefGoogle Scholar
Delfosse, V, Grimaldi, M, le Maire, A et al. (2014) Nuclear receptor profiling of bisphenol-A and its halogenated analogues. Vitam Horm 94, 229–251. doi: 10.1016/B978-0-12-800095-3.00009-2.CrossRefGoogle ScholarPubMed
Gonsioroski, A, Mourikes, VE & Flaws, JA (2020) Endocrine disruptors in water and their effects on the reproductive system. Int J Mol Sci 21, 1929. doi: 10.3390/ijms21061929
CrossRefGoogle ScholarPubMed
Gao, H, Yang, BJ, Li, N et al. (2015) Bisphenol A and hormone-associated cancers: current progress and perspectives. Med (Baltimore) 94, e211. doi: 10.1097/MD.0000000000000211.CrossRefGoogle Scholar
Rebuli, ME, Cao, J, Sluzas, E et al. (2014) Investigation of the effects of subchronic low dose oral exposure to bisphenol A (BPA) and ethinyl estradiol (EE) on estrogen receptor expression in the juvenile and adult female rat hypothalamus. Toxicol Sci 140, 190–203. doi: 10.1093/toxsci/kfu074.CrossRefGoogle ScholarPubMed
Song, M, Liang, D, Liang, Y et al. (2014) Assessing developmental toxicity and estrogenic activity of halogenated bisphenol A on zebrafish (Danio rerio). Chemosphere 112, 275–281. doi: 10.1016/j.chemosphere.2014.04.084.CrossRefGoogle ScholarPubMed
Brotons, JA, Olea-Serrano, MF, Villalobos, M et al. (1995) Xenoestrogens released from lacquer coatings in food cans. Environ Health Perspect 103, 608–612. doi: 10.1289/ehp.95103608.CrossRefGoogle ScholarPubMed
Steinmetz, R, Mitchner, NA, Grant, A et al. (1998) The xenoestrogen bisphenol A induces growth, differentiation, and c-fos gene expression in the female reproductive tract. Endocrinology 139, 2741–2747. doi: 10.1210/endo.139.6.6027.CrossRefGoogle ScholarPubMed
Das, S & Thomas, P (1999) Pesticides interfere with the nongenomic action of a progestogen on meiotic maturation by binding to its plasma membrane receptor on fish oocytes. Endocrinology 140, 1953–1956. doi: 10.1210/endo.140.4.6781.CrossRefGoogle ScholarPubMed
Soundararajan, A, Prabu, P, Mohan, V et al. (2019) Novel insights of elevated systemic levels of bisphenol-A (BPA) linked to poor glycemic control, accelerated cellular senescence and insulin resistance in patients with type 2 diabetes. Mol Cell Biochem 458, 171–183. doi: 10.1007/s11010-019-03540-9
CrossRefGoogle ScholarPubMed
Gong, H, Zhang, X, Cheng, B et al. (2013) Bisphenol A accelerates toxic amyloid formation of human islet amyloid polypeptide: a possible link between bisphenol A exposure and type 2 diabetes. PLoS One 8, e54198. doi: 10.1371/journal.pone.0054198
CrossRefGoogle ScholarPubMed
Chen, J, Zhong, L, Wu, J et al. (2018) A murine pancreatic islet cell-based screening for diabetogenic environmental chemicals. J Vis Exp 136, 57327. doi: 10.3791/57327
Google Scholar
Jiang, W, Ding, K, Huang, W et al. (2023) Potential effects of bisphenol A on diabetes mellitus and its chronic complications: a narrative review. Heliyon 9, e16340. doi: 10.1016/j.heliyon.2023.e16340
CrossRefGoogle ScholarPubMed
Nadal, A (2013) Obesity: fat from plastics? Linking bisphenol A exposure and obesity. Nat Rev Endocrinol 9, 9–10. doi: 10.1038/nrendo.2012.205
CrossRefGoogle ScholarPubMed
Moreno-Gómez-Toledano, R, Arenas, MI, Muñoz-Moreno, C et al. (2022) Comparison of the renal effects of bisphenol A in mice with and without experimental diabetes. Role of sexual dimorphism. Biochim Biophys Acta Mol Basis Dis 1868, 166296. doi: 10.1016/j.bbadis.2021.166296
CrossRefGoogle ScholarPubMed
Bulzomi, P & Marino, M (2011) Environmental endocrine disruptors: does a sex-related susceptibility exist? Front Biosci (Landmark Ed) 16, 2478–2498. doi: 10.2741/3867.CrossRefGoogle ScholarPubMed
Bolli, A & Marino, M (2011) Current and future development of estrogen receptor ligands: applications in estrogen-related cancers. Recent Pat Endocr Metab Immune Drug Discov 5, 210–229. doi: 10.2174/187221411797265881.CrossRefGoogle ScholarPubMed
Wang, LH, Chen, LR & Chen, KH (2021) In vitro and vivo identification, metabolism and action of xenoestrogens: an overview. Int J Mol Sci 22, 4013. doi: 10.3390/ijms22084013.CrossRefGoogle ScholarPubMed
Song, Y, Chou, EL, Baecker, A et al. (2016) Endocrine-disrupting chemicals, risk of type 2 diabetes, and diabetes-related metabolic traits: a systematic review and meta-analysis. J Diabetes 8, 516–532. doi: 10.1111/1753-0407.12325
CrossRefGoogle ScholarPubMed
Gore, AC, Chappell, VA, Fenton, SE et al. (2015) Executive summary to EDC-2: the endocrine society’s second scientific statement on endocrine-disrupting chemicals. Endocr Rev 36, 593–602. doi: 10.1210/er.2015-1093
CrossRefGoogle ScholarPubMed
Vabre, P, Gatimel, N, Moreau, J et al. (2017) Environmental pollutants, a possible etiology for premature ovarian insufficiency: a narrative review of animal and human data. Environ Health 16, 37. doi: 10.1186/s12940-017-0242-4
CrossRefGoogle ScholarPubMed
Götz, F, Thieme, S & Dörner, G (2001) Female infertility--effect of perinatal xenoestrogen exposure on reproductive functions in animals and humans. Folia Histochem Cytobiol 2, 40–43.Google Scholar
Grindler, NM, Allsworth, JE, Macones, GA et al. (2011) Persistent organic pollutants and early menopause in U.S. women. PLoS One. Bolli A, Marino M. Current and future development of estrogen receptor ligands: applications in estrogen-related cancers. Recent Pat Endocr Metab Immune Drug Discov 5, 210–229. doi: 10.2174/187221411797265881.Google Scholar
Carwile, JL & Michels, KB (2011) Urinary bisphenol A and obesity: NHANES 2003–2006. Environ Res 111, 825–830. doi: 10.1016/j.envres.2011.05.014
CrossRefGoogle Scholar
Riffee, JNJ, Wade, M, Sine, T et al. (2023) The link of environmental estrogens exposure to oxidative stress and their association with insulin- and exercise-induced glucose uptake. Obes Med 42, 100503. doi: 10.1016/j.obmed.2023.100503.CrossRefGoogle Scholar
Paterni, I, Granchi, C & Minutolo, F (2017) Risks and benefits related to alimentary exposure to xenoestrogens. Crit Rev Food Sci Nutr 57, 3384–3404. doi: 10.1080/10408398.2015.1126547.CrossRefGoogle ScholarPubMed
Palmlund, I (1996) Exposure to a xenoestrogen before birth: the diethylstilbestrol experience. J Psychosom Obstet Gynaecol 17, 71–84. doi: 10.3109/01674829609025667.CrossRefGoogle ScholarPubMed
Vilahur, N, Bustamante, M, Byun, HM et al. (2014) Prenatal exposure to mixtures of xenoestrogens and repetitive element DNA methylation changes in human placenta. Environ Int 71, 81–87. doi: 10.1016/j.envint.2014.06.006.CrossRefGoogle ScholarPubMed
García-Arevalo, M, Alonso-Magdalena, P, Rebelo Dos Santos, J et al. (2014) Exposure to bisphenol-A during pregnancy partially mimics the effects of a high-fat diet altering glucose homeostasis and gene expression in adult male mice. PLoS One 9, e100214. doi: 10.1371/journal.pone.0100214
CrossRefGoogle ScholarPubMed
Miura, R, Araki, A, Minatoya, M et al. (2019) An epigenome-wide analysis of cord blood DNA methylation reveals sex-specific effect of exposure to bisphenol A. Sci Rep 9, 12369. doi: 10.1038/s41598-019-48916-5
CrossRefGoogle ScholarPubMed
Yang, CZ, Yaniger, SI, Jordan, VC et al. (2011) Most plastic products release estrogenic chemicals: a potential health problem that can be solved. Environ Health Perspect 119, 989–996. doi: 10.1289/ehp.1003220.CrossRefGoogle ScholarPubMed
Bittner, GD, Yang, CZ & Stoner, MA (2014) Estrogenic chemicals often leach from BPA-free plastic products that are replacements for BPA-containing polycarbonate products. Environ Health 13, 41. doi: 10.1186/1476-069X-13-41.CrossRefGoogle ScholarPubMed
Darnerud, PO, Eriksen, GS, Jóhannesson, T et al. (2001) Polybrominated diphenyl ethers: occurrence, dietary exposure, and toxicology. Environ Health Perspect 109, 49–68. doi: 10.1289/ehp.01109s149
CrossRefGoogle Scholar
Hites, RA, Foran, JA, Schwager, SJ et al. (2004) Global assessment of polybrominated diphenyl ethers in farmed and wild salmon. Environ Sci Technol 38, 4945–4949. doi: 10.1021/es049548m
CrossRefGoogle ScholarPubMed
Yokoyama, M, Origasa, H, Matsuzaki, M et al. (2007) Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 369, 1090–1098. doi: 10.1016/S0140-6736(07)60527-3. (published correction appears in Lancet. 2007 Jul 21 370(9583):220).CrossRefGoogle Scholar
Troesch, B, Eggersdorfer, M, Laviano, A et al. (2020) Expert opinion on benefits of long-chain n-3 fatty acids (DHA and EPA) in aging and clinical nutrition. Nutrients 12, 2555. doi: 10.3390/nu12092555
CrossRefGoogle ScholarPubMed
Hibbeln, JR, Davis, JM, Steer, C et al. (2007) Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study. Lancet 369, 578–585. doi: 10.1016/S0140-6736(07)60277-3
CrossRefGoogle ScholarPubMed
Davidson, PW, Myers, GJ, Cox, C et al. (1995) Longitudinal neurodevelopmental study of Seychellois children following in utero exposure to methylmercury from maternal fish ingestion: outcomes at 19 and 29 months. Neurotoxicology 16, 677–688.Google Scholar
Myers, GJ, Davidson, PW, Cox, C et al. (2003) Prenatal methylmercury exposure from ocean fish consumption in the Seychelles child development study. Lancet 361, 1686–1692. doi: 10.1016/S0140-6736(03)13371-5
CrossRefGoogle ScholarPubMed
Mukherjee, R, Pandya, P, Baxi, D et al. (2021) Endocrine disruptors-‘food’ for thought. Proc Zool Soc 74, 432–442. doi: 10.1007/s12595-021-00414-1
CrossRefGoogle ScholarPubMed
Lee, A, Bensaada, S, Lamothe, V et al. (2022) Endocrine disruptors on and in fruits and vegetables: estimation of the potential exposure of the French population. Food Chem 373, 131513. doi: 10.1016/j.foodchem.2021.131513
CrossRefGoogle ScholarPubMed
Kuiper, GG, Lemmen, JG, Carlsson, B et al. (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139, 4252–4263. doi: 10.1210/endo.139.10.6216.CrossRefGoogle ScholarPubMed