Potential Molecular Mechanisms of Bisphenol A in Obesity Development Bisphenol A and obesity
International Journal of Medical Toxicology and Forensic Medicine,
Vol. 13 No. 4 (2023),
14 December 2023
https://doi.org/10.32598/ijmtfm.v13i4.43484
Abstract
Bisphenol A (BPA), an endocrine disruptor, is associated with metabolic disorders. However, several studies have suggested that exposure to BPA can cause obesity. It has recently got more attention from scientists as a risk factor for obesity due to its ability to mimic natural estrogens and bind to their receptors. Nonetheless, the molecular mechanism underpinning the environmental etiology of metabolic disorders has not been not fully clarified. In this regard, BPA exposure directly disrupts endocrine regulation, neuroimmune and signaling pathways, and gut microbes, resulting in obesity. In addition, epidemiological studies have revealed a significant relationship between BPA exposure and the development of obesity, although conflicting results have been reported. Therefore, this review summarized the possible role and molecular mechanisms associated with BPA exposure that may lead to obesity based on in vivo and in vivo studies.
How to Cite
References
Lobstein T, Jackson-Leach R, Moodie ML, Hall KD, Gortmaker SL, Swinburn BA, et al. Child and adolescent obesity: Part of a bigger picture. Lancet (London, England). 2015; 385(9986):2510-20. [DOI:10.1016/S0140-6736(14)61746-3] [PMID]
Simmonds M, Llewellyn A, Owen CG, Woolacott N. Predicting adult obesity from childhood obesity: A systematic review and meta-analysis. Obesity Reviews. 2016; 17(2):95-107. [DOI:10.1111/obr.12334] [PMID]
Naomi R, Yazid MD, Bahari H, Keong YY, Rajandram R, Embong H, et al. Bisphenol A (BPA) leading to obesity and cardiovascular complications: A compilation of current in vivo study. International Journal of Molecular Sciences. 2022; 23(6):2969. [DOI:10.3390/ijms23062969] [PMID]
Wang Z, Liu H, Liu S. Low-dose bisphenol A exposure: A seemingly instigating carcinogenic effect on breast cancer. Advanced Science (Weinheim, Baden-Wurttemberg, Germany). 2017; 4(2):1600248. [DOI:10.1002/advs.201600248] [PMID]
Rönn M, Kullberg J, Karlsson H, Berglund J, Malmberg F, Orberg J, et al. Bisphenol A exposure increases liver fat in juvenile fructose-fed fischer 344 rats. Toxicology. 2013; 303:125-32. [DOI:10.1016/j.tox.2012.09.013] [PMID]
Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, et al. EDC-2: The Endocrine Society’s second scientific statement on endocrine-disrupting chemicals. Endocrine Reviews. 2015; 36(6):E1-150. [DOI:10.1210/er.2015-1010] [PMID]
Groshart C, Okkeman P, Pijnenburg A. Chemical study on bisphenol A. Jeddah: Rijksinstituut voor Kust en Zee/RIKZ; 2001. [Link]
Oldring PK, Castle L, O'Mahony C, Dixon J. Estimates of dietary exposure to bisphenol A (BPA) from light metal packaging using food consumption and packaging usage data: A refined deterministic approach and a fully probabilistic (FACET) approach. Food additives & contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment. 2014; 31(3):466-89. [DOI:10.1080/19440049.2013.860240] [PMID]
Goodman J, Rhomberg L. 16 - Bisphenol A. In: Shaw I, editor. Endocrine-disrupting chemicals in food: Woodhead publishing series in food science, technology and nutrition. Amsterdam: Elsevier; 2009. [DOI:10.1533/9781845695743.4.406]
Rahman MS, Adegoke EO, Pang MG. Drivers of owning more BPA. Journal of Hazardous Materials. 2021; 417:126076. [DOI:10.1016/j.jhazmat.2021.126076] [PMID]
Carwile JL, Ye X, Zhou X, Calafat AM, Michels KB. Canned soup consumption and urinary bisphenol A: A randomized crossover trial. JAMA. 2011; 306(20):2218-20. [DOI:10.1001/jama.2011.1721] [PMID]
Elobeid MA, Almarhoon ZM, Virk P, Hassan ZK, Omer SA, ElAmin M, et al. Bisphenol A detection in various brands of drinking bottled water in Riyadh, Saudi Arabia using gas chromatography/mass spectrometer. Tropical Journal of Pharmaceutical Research. 2012;11(3):455-9. [DOI:10.4314/tjpr.v11i3.15]
Ehrlich S, Calafat AM, Humblet O, Smith T, Hauser R. Handling of thermal receipts as a source of exposure to bisphenol A. JAMA. 2014; 311(8):859-60. [DOI:10.1001/jama.2013.283735] [PMID]
Rudel RA, Brody JG, Spengler JD, Vallarino J, Geno PW, Sun G, et al. Identification of selected hormonally active agents and animal mammary carcinogens in commercial and residential air and dust samples. Journal of the Air & Waste Management Association. 2001; 51(4):499-513. [DOI:10.1080/10473289.2001.10464292] [PMID]
Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism. 2019; 92:6-10. [DOI:10.1016/j.metabol.2018.09.005] [PMID]
GBD 2015 Eastern Mediterranean Region Obesity Collaborators. Burden of obesity in the Eastern Mediterranean Region: Findings from the global burden of disease 2015 study. International Journal of Public Health. 2018; 63(Suppl 1):165-76. [DOI:10.1007/s00038-017-1002-5] [PMID]
Gill TP. Cardiovascular risk in the Asia-Pacific region from a nutrition and metabolic point of view: Abdominal obesity. Asia Pacific Journal of Clinical Nutrition. 2001; 10(2):85-9. [DOI:10.1111/j.1440-6047.2001.00231.x] [PMID]
Nehus E. Obesity and chronic kidney disease. Current Opinion in Pediatrics. 2018; 30(2):241-6. [DOI:10.1097/MOP.0000000000000586] [PMID]
Chamorro-Garcia R, Blumberg B. Current research approaches and challenges in the obesogen field. Frontiers in Endocrinology. 2019; 10:167. [DOI:10.3389/fendo.2019.00167] [PMID]
Braun JM. Early-life exposure to EDCs: Role in childhood obesity and neurodevelopment. Nature Reviews Endocrinology. 2017; 13(3):161-73. [DOI:10.1038/nrendo.2016.186] [PMID]
Li J, Lai H, Chen S, Zhu H, Lai S. Gender differences in the associations between urinary bisphenol A and body composition among American children: The national health and nutrition examination survey, 2003-2006. Journal of Epidemiology. 2017; 27(5):228-34. [DOI:10.1016/j.je.2016.12.001] [PMID]
Liu B, Lehmler HJ, Sun Y, Xu G, Sun Q, Snetselaar LG, et al. Association of bisphenol A and its substitutes, bisphenol F and bisphenol S, with obesity in United States children and adolescents. Diabetes & Metabolism Journal. 2019; 43(1):59-75. [DOI:10.4093/dmj.2018.0045] [PMID]
Liu B, Lehmler HJ, Sun Y, Xu G, Liu Y, Zong G, et al. Bisphenol A substitutes and obesity in US adults: Analysis of a population-based, cross-sectional study. The Lancet. Planetary Health. 2017; 1(3):e114-22. [DOI:10.1016/S2542-5196(17)30049-9] [PMID]
Zhang Y, Dong T, Hu W, Wang X, Xu B, Lin Z, et al. Association between exposure to a mixture of phenols, pesticides, and phthalates and obesity: Comparison of three statistical models. Environment International. 2019; 123:325-36. [DOI:10.1016/j.envint.2018.11.076] [PMID]
Nunez AA, Kannan K, Giesy JP, Fang J, Clemens LG. Effects of bisphenol A on energy balance and accumulation in brown adipose tissue in rats. Chemosphere. 2001; 42(8):917-22. [DOI:10.1016/S0045-6535(00)00196-X] [PMID]
Wang T, Li M, Chen B, Xu M, Xu Y, Huang Y, et al. Urinary bisphenol A (BPA) concentration associates with obesity and insulin resistance. The Journal of Clinical Endocrinology & Metabolism. 2012; 97(2):E223-7. [DOI:10.1210/jc.2011-1989] [PMID]
Ko A, Hwang MS, Park JH, Kang HS, Lee HS, Hong JH. Association between urinary bisphenol A and waist circumference in Korean adults. Toxicological Research. 2014; 30(1):39-44. [DOI:10.5487/TR.2014.30.1.039] [PMID]
Yang J, Eliasson B, Smith U, Cushman SW, Sherman AS. The size of large adipose cells is a predictor of insulin resistance in first-degree relatives of type 2 diabetic patients. Obesity (Silver Spring, Md.). 2012; 20(5):932-8. [DOI:10.1038/oby.2011.371] [PMID]
Masuno H, Kidani T, Sekiya K, Sakayama K, Shiosaka T, Yamamoto H, et al. Bisphenol A in combination with insulin can accelerate the conversion of 3T3-L1 fibroblasts to adipocytes. Journal of Lipid Research. 2002; 43(5):676-84. [DOI:10.1016/S0022-2275(20)30108-5] [PMID]
Sargis RM, Johnson DN, Choudhury RA, Brady MJ. Environmental endocrine disruptors promote adipogenesis in the 3T3-L1 cell line through glucocorticoid receptor activation. Obesity (Silver Spring, Md.). 2010; 18(7):1283-8. [DOI:10.1038/oby.2009.419] [PMID]
Ben-Jonathan N, Hugo ER, Brandebourg TD. Effects of bisphenol A on adipokine release from human adipose tissue: Implications for the metabolic syndrome. Molecular and Cellular Endocrinology. 2009; 304(1-2):49-54. [DOI:10.1016/j.mce.2009.02.022] [PMID]
Hiroi T, Okada K, Imaoka S, Osada M, Funae Y. Bisphenol A binds to protein disulfide isomerase and inhibits its enzymatic and hormone-binding activities. Endocrinology. 2006; 147(6):2773-80. [DOI:10.1210/en.2005-1235] [PMID]
Ariemma F, D'Esposito V, Liguoro D, Oriente F, Cabaro S, Liotti A, et al. Low-dose bisphenol-A impairs adipogenesis and generates dysfunctional 3T3-L1 adipocytes. PloS One. 2016; 11(3):e0150762. [DOI:10.1371/journal.pone.0150762] [PMID]
González-Casanova JE, Bermúdez V, Caro Fuentes NJ, Angarita LC, Caicedo NH, Rivas Muñoz J, et al. New evidence on BPA’s role in adipose tissue development of proinflammatory processes and its relationship with obesity.International Journal of Molecular Sciences.2023; 24(9):8231. [PMID]
Longo M, Zatterale F, Naderi J, Nigro C, Oriente F, Formisano P, et al. Low-dose Bisphenol-A promotes epigenetic changes at Pparγ promoter in adipose precursor cells. Nutrients. 2020; 12(11):3498. [DOI:10.3390/nu12113498] [PMID]
Hong X, Zhou Y, Zhu Z, Li Y, Li Z, Zhang Y, et al. Environmental endocrine disruptor bisphenol A induces metabolic derailment and obesity via upregulating IL-17A in adipocytes. Environment International. 2023; 172:107759. [DOI:10.1016/j.envint.2023.107759] [PMID]
Rubin BS, Murray MK, Damassa DA, King JC, Soto AMJEhp. Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels. Environmental Health Perspectives. 2001; 109(7):675-80. [DOI:10.1289/ehp.01109675] [PMID]
Kwintkiewicz J, Nishi Y, Yanase T, Giudice LC. Peroxisome proliferator–activated receptor-γ mediates bisphenol A inhibition of FSH-stimulated IGF-1, aromatase, and estradiol in human granulosa cells. Environmental Health Perspectives. 2010; 118(3):400-6. [PMID]
Pereira-Fernandes A, Demaegdt H, Vandermeiren K, Hectors TL, Jorens PG, Blust R, et al. Evaluation of a screening system for obesogenic compounds: Screening of endocrine disrupting compounds and evaluation of the PPAR dependency of the effect. PLOS ONE. 2013; 8(10):e77481. [PMID]
Ahmed S, Atlas E. Bisphenol S-and bisphenol A-induced adipogenesis of murine preadipocytes occurs through direct peroxisome proliferator-activated receptor gamma activation. International Journal of Obesity. 2016; 40(10):1566-73. [PMID]
Drobna Z, Talarovicova A, Schrader HE, Fennell TR, Snyder RW, Rissman EF. Bisphenol F has different effects on preadipocytes differentiation and weight gain in adult mice as compared with Bisphenol A and S. Toxicology. 2019; 420:66-72. [PMID]
Junge KM, Leppert B, Jahreis S, Wissenbach DK, Feltens R, Grützmann K, et al. MEST mediates the impact of prenatal bisphenol A exposure on long-term body weight development. ClinIcal Epigenetics. 2018; 10:58. [DOI:10.1186/s13148-018-0478-z] [PMID]
Kidani T, Kamei S, Miyawaki J, Aizawa J, Sakayama K, Masuno H. Bisphenol A downregulates Akt signaling and inhibits adiponectin production and secretion in 3T3-L1 adipocytes. Journal of Atherosclerosis and Thrombosis. 2010; 17(8):834-43. [PMID]
Héliès-Toussaint C, Peyre L, Costanzo C, Chagnon MC, Rahmani R. Is bisphenol S a safe substitute for bisphenol A in terms of metabolic function? An in vitro study.Toxicology and Applied Pharmacology. 2014; 280(2):224-35. [PMID]
Angle BM, Do RP, Ponzi D, Stahlhut RW, Drury BE, Nagel SC, et al. Metabolic disruption in male mice due to fetal exposure to low but not high doses of bisphenol A (BPA): Evidence for effects on body weight, food intake, adipocytes, leptin, adiponectin, insulin and glucose regulation. Reproductive Toxicology. 2013; 42:256-68. [PMID]
Wei J, Lin Y, Li Y, Ying C, Chen J, Song L, et al. Perinatal exposure to bisphenol A at reference dose predisposes offspring to metabolic syndrome in adult rats on a high-fat diet. Endocrinology. 2011; 152(8):3049-61. [PMID]
Alonso-Magdalena P, Vieira E, Soriano S, Menes L, Burks D, Quesada I, et al. Bisphenol A exposure during pregnancy disrupts glucose homeostasis in mothers and adult male offspring. Environmental Health Perspectives. 2010; 118(9):1243-50. [DOI:10.1289/ehp.1001993] [PMID]
Boudalia S, Berges R, Chabanet C, Folia M, Decocq L, Pasquis B, et al. A multi-generational study on low-dose BPA exposure in Wistar rats: effects on maternal behavior, flavor intake and development. Neurotoxicology and Teratology. 2014; 41:16-26. [DOI:10.1016/j.ntt.2013.11.002] [PMID]
Ryan KK, Haller AM, Sorrell JE, Woods SC, Jandacek RJ, Seeley RJ. Perinatal exposure to bisphenol-a and the development of metabolic syndrome in CD-1 mice. Endocrinology. 2010; 151(6):2603-12. [PMID]
Van Esterik J, Dollé M, Lamoree M, Van Leeuwen S, Hamers T, Legler J, et al. Programming of metabolic effects in C57BL/6JxFVB mice by exposure to bisphenol A during gestation and lactation. Toxicology. 2014; 321:40-52. [PMID]
Gao L, Wang HN, Zhang L, Peng FY, Jia Y, Wei W, et al. Effect of perinatal bisphenol A exposure on serum lipids and lipid enzymes in offspring rats of different sex. Biomedical and Environmental Sciences : BES. 2016; 29(9):686-9. [PMID]
Rubin BS, Paranjpe M, DaFonte T, Schaeberle C, Soto AM, Obin M, et al. Perinatal BPA exposure alters body weight and composition in a dose specific and sex specific manner: The addition of peripubertal exposure exacerbates adverse effects in female mice. Reproductive Toxicology. 2017; 68:130-44. [PMID]
Meng Z, Wang D, Yan S, Li R, Yan J, Teng M, et al. Effects of perinatal exposure to BPA and its alternatives (BPS, BPF and BPAF) on hepatic lipid and glucose homeostasis in female mice adolescent offspring. Chemosphere. 2018; 212:297-306. [PMID]
Shih MK, Tain YL, Chen YW, Hsu WH, Yeh YT, Chang SKC, et al.Resveratrol butyrate esters inhibit obesity caused by perinatal exposure to bisphenol A in female offspring rats.Molecules. 2021; 26(13):4010. [DOI:10.3390/molecules26134010] [PMID]
Taylor JA, Shioda K, Mitsunaga S, Yawata S, Angle BM, Nagel SC, et al. Prenatal exposure to bisphenol A disrupts naturally occurring bimodal dna methylation at proximal promoter of fggy, an obesity-relevant gene encoding a Carbohydrate kinase, in gonadal white adipose tissues of CD-1 mice. Endocrinology. 2018; 159(2):779-94. [PMID]
Lin R, Jia Y, Wu F, Meng Y, Sun Q, Jia L. Combined exposure to fructose and bisphenol A exacerbates abnormal lipid metabolism in liver of developmental male rats. International Journal of Environmental Research and Public Health. 2019; 16(21):4152. [PMID]
Neier K, Marchlewicz EM, Bedrosian LD, Dolinoy DC, Harris C. Characterization of the mouse white adipose tissue redox environment and associations with perinatal environmental exposures to bisphenol A and high-fat diets. The Journal of Nutritional Biochemistry. 2019; 66:86–97. [DOI:10.1016/j.jnutbio.2019.01.005] [PMID]
- Abstract Viewed: 306 times
- pdf Downloaded: 239 times