Mechanisms of obesogens and their impact on adipose tissue, hormones, and inflammation

Taiwo Ogunjobi; Charles Omiyale; Tolulope Gbayisomore; Oluwatoyin Olofin; Patricia Nneji; Damilola Onikeku; Moses Oluwole; Somtochukwu Ezeano; Dayo Soleye; Dasola Fadipe; Samson Fakojo; Tobi Sulaiman; Rufus Ajayi

doi:10.20883/medical.e965

Authors

Taiwo Ogunjobi Faculty of Basic Medical Sciences, Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomosho, Oyo State, Nigeria https://orcid.org/0009-0006-8125-7933
Charles Omiyale Department of Pharmacology, Toxicology and Therapeutics. Faculty of Basic Medical Sciences. College of Medicine. University of Lagos. Nigeria https://orcid.org/0000-0002-4951-3881
Tolulope Gbayisomore University of Benin Teaching Hospital, Benin city, Edo state https://orcid.org/0000-0001-8210-4054
Oluwatoyin Olofin Department of Biochemistry, school of life science, Federal University of Technology Akure, Ondo State, Nigeria https://orcid.org/0009-0003-2967-2417
Patricia Nneji Faculty of Education, Department of Science (Biology) Education, Niger Delta University https://orcid.org/0009-0008-7007-903X
Damilola Onikeku Department of Health Promotion and Environmental Health Education, University of Ilorin, Ilorin Kwara State https://orcid.org/0009-0000-6590-7234
Moses Oluwole Department of Health Promotion and Environmental Health Education, University of Ilorin, Ilorin Kwara State, Nigeria https://orcid.org/0009-0007-3791-5166
Somtochukwu Ezeano Department of Anatomy, University of Medical Sciences, Ondo State. Nigeria https://orcid.org/0009-0001-1530-6286
Dayo Soleye Food Science and Technology, Faculty of Agriculture Science, Nnamdi Azikiwe University, Nigeria https://orcid.org/0009-0003-6317-784X
Dasola Fadipe Department of Biochemistry, Faculty of Basic Medical sciences, Lautech, Ogbomosho Oyo State, Nigeria https://orcid.org/0009-0002-7889-2590
Samson Fakojo Faculty of clinical sciences, department of Medicine, Ladoke Akintola University of Technology Ogbo-mosho, Oyo state, Nigeria https://orcid.org/0009-0005-2980-1412
Tobi Sulaiman Department of Biochemistry, Faculty of Basic Medical sciences, Lautech, Ogbomosho Oyo State, Nige-ria https://orcid.org/0009-0005-7390-9156
Rufus Ajayi University of Illinois Springfield, Illinois, USA https://orcid.org/0009-0003-3386-1317

DOI:

https://doi.org/10.20883/medical.e965

Keywords:

endocrine disruptors, obesity, hormone regulation, metabolic dysfunction, environmental factors, chemical exposures

Abstract

The complex interactions of genetic, environmental, and behavioral factors that contribute to obesity, a pervasive global health issue, continue to be a severe concern for people all over the world. This manuscript examines the field of obesogen research, seeking to understand the mechanisms by which certain environmental chemicals contribute to the development of obesity. We explore the obesogenic effects by focusing on pathways such as inflammation, hormone interference, and the activation of peroxisome proliferator-activated receptors (PPARs). The text focuses on the significance of PPAR isoforms, especially PPARγ, and how they play a role in adipose tissue growth. We examine how obesogens such as tributyltin (TBT) and bisphenol A (BPA) influence these receptors. Additionally, we examined the impact of obesogens on hormonal regulation, including disruptions to leptin and adiponectin, and investigated the intricate relationship between chronic inflammation and obesity. In the methodology of our study, we utilized a systematic search to identify peer-reviewed articles of relevance. This search spanned various model systems, including in vitro, in vivo, and epidemiological studies, providing insights into the distinct advantages and limitations associated with each. Epigenetic modifications and the influence of obesogens on the development of adipose tissue, metabolism, and appetite control further enrich our understanding of this complex field. Finally, we assess the role of endocrine disruptors in amplifying the risk of obesity, emphasizing the heightened susceptibility during crucial developmental periods. This comprehensive review aims to contribute to the ongoing discourse surrounding obesogens, paving the way for targeted interventions and a more profound comprehension of the global obesity epidemic.

Downloads

Download data is not yet available.

Author Biographies

Charles Omiyale, Department of Pharmacology, Toxicology and Therapeutics. Faculty of Basic Medical Sciences. College of Medicine. University of Lagos. Nigeria

Reseacher, Department of Pharmacology, Toxicology and Therapeutics. Faculty of Basic Medical Sciences. College of Medicine. University of Lagos. Nigeria

Tolulope Gbayisomore, University of Benin Teaching Hospital, Benin city, Edo state

Researcher, Data Intelligence and Scientific Innovation, University of Benin Teaching Hospital, Benin city, Edo state, Nigeria.

References

Heindel JJ, Blumberg B. Environmental obesogens: Mechanisms and controversies. Annu Rev Pharmacol Toxicol [Internet]. 2019;59(1):89–106. Available from: http://dx.doi.org/10.1146/annurev-pharmtox-010818-021304. DOI: https://doi.org/10.1146/annurev-pharmtox-010818-021304

Ribeiro CM, Beserra BTS, Silva NG, Lima CL, Rocha PRS, Coelho MS, et al. Exposure to endocrine-disrupting chemicals and anthropometric measures of obesity: a systematic review and meta-analysis. BMJ Open [Internet]. 2020;10(6):e033509. Available from: http://dx.doi.org/10.1136/bmjopen-2019-033509. DOI: https://doi.org/10.1136/bmjopen-2019-033509

Heindel JJ, Blumberg B, Cave M, Machtinger R, Mantovani A, Mendez MA, et al. Metabolism disrupting chemicals and metabolic disorders. Reprod Toxicol [Internet]. 2017;68:3–33. Available from: http://dx.doi.org/10.1016/j.reprotox.2016.10.001. DOI: https://doi.org/10.1016/j.reprotox.2016.10.001

Gupta R, Kumar P, Fahmi N, Garg B, Dutta S, Sachar S, et al. Endocrine disruption and obesity: A current review on environmental obesogens. Current Research in Green and Sustainable Chemistry [Internet]. 2020;3(100009):100009. Available from: http://dx.doi.org/10.1016/j.crgsc.2020.06.002. DOI: https://doi.org/10.1016/j.crgsc.2020.06.002

Ruhlen RL, Howdeshell KL, Mao J, Taylor JA, Bronson FH, Newbold RR, et al. Low phytoestrogen levels in feed increase fetal serum estradiol resulting in the “fetal estrogenization syndrome” and obesity in CD-1 mice. Environ Health Perspect [Internet]. 2008;116(3):322–8. Available from: http://dx.doi.org/10.1289/ehp.10448. DOI: https://doi.org/10.1289/ehp.10448

De Araújo JFP, Podratz PL, Sena GC, Merlo E, Freitas-Lima LC, Ayub JGM, et al. The obesogen tributyltin induces abnormal ovarian adipogenesis in adult female rats. Toxicol Lett [Internet]. 2018;295:99–114. Available from: http://dx.doi.org/10.1016/j.toxlet.2018.06.1068. DOI: https://doi.org/10.1016/j.toxlet.2018.06.1068

Lima MS, Perez GS, Morais GL, Santos LS, Cordeiro GS, Couto RD, et al. Effects of maternal high fat intake during pregnancy and lactation on total cholesterol and adipose tissue in neonatal rats. Braz J Biol [Internet]. 2018;78(4):615–8. Available from: http://dx.doi.org/10.1590/1519-6984.166788. DOI: https://doi.org/10.1590/1519-6984.166788

Azad MB, Archibald A, Tomczyk MM, Head A, Cheung KG, de Souza RJ, et al. Nonnutritive sweetener consumption during pregnancy, adiposity, and adipocyte differentiation in offspring: evidence from humans, mice, and cells. Int J Obes (Lond) [Internet]. 2020;44(10):2137–48. Available from: http://dx.doi.org/10.1038/s41366-020-0575-x. DOI: https://doi.org/10.1038/s41366-020-0575-x

Chamorro-Garcia R, Diaz-Castillo C, Shoucri BM, Käch H, Leavitt R, Shioda T, et al. Ancestral perinatal obesogen exposure results in a transgenerational thrifty phenotype in mice. Nat Commun [Internet]. 2017;8(1). Available from: http://dx.doi.org/10.1038/s41467-017-01944-z. DOI: https://doi.org/10.1038/s41467-017-01944-z

Braakhuis HM, Slob W, Olthof ED, Wolterink G, Zwart EP, Gremmer ER, et al. Is current risk assessment of non-genotoxic carcinogens protective? Crit Rev Toxicol [Internet]. 2018;48(6):500–11. Available from: http://dx.doi.org/10.1080/10408444.2018.1458818. DOI: https://doi.org/10.1080/10408444.2018.1458818

Nilsson EE, Sadler-Riggleman I, Skinner MK. Environmentally induced epigenetic transgenerational inheritance of disease. Environ Epigenet [Internet]. 2018;4(2). Available from: http://dx.doi.org/10.1093/eep/dvy016. DOI: https://doi.org/10.1093/eep/dvy016

Amin MN, Hussain MS, Sarwar MS, Rahman Moghal MM, Das A, Hossain MZ, et al. How the association between obesity and inflammation may lead to insulin resistance and cancer. Diabetes Metab Syndr [Internet]. 2019;13(2):1213–24. Available from: http://dx.doi.org/10.1016/j.dsx.2019.01.041. DOI: https://doi.org/10.1016/j.dsx.2019.01.041

André A, Ruivo R, Fonseca E, Froufe E, Castro LFC, Santos MM. The retinoic acid receptor (RAR) in molluscs: Function, evolution and endocrine disruption insights. Aquat Toxicol [Internet]. 2019;208:80–9. Available from: http://dx.doi.org/10.1016/j.aquatox.2019.01.002. DOI: https://doi.org/10.1016/j.aquatox.2019.01.002

Mousavi MS, Shahverdi A, Drevet J, Akbarinejad V, Esmaeili V, Sayahpour FA, et al. Peroxisome Proliferator-Activated Receptors (PPARs) levels in spermatozoa of normozoospermic and asthenozoospermic men. Syst Biol Reprod Med [Internet]. 2019;65(6):409–19. Available from: http://dx.doi.org/10.1080/19396368.2019.1677801. DOI: https://doi.org/10.1080/19396368.2019.1677801

Perez VM, Gabell J, Behrens M, Wase N, DiRusso CC, Black PN. Deletion of fatty acid transport protein 2 (FATP2) in the mouse liver changes the metabolic landscape by increasing the expression of PPARα-regulated genes. J Biol Chem [Internet]. 2020;295(17):5737–50. Available from: http://dx.doi.org/10.1074/jbc.ra120.012730. DOI: https://doi.org/10.1074/jbc.RA120.012730

Choi J-M, Bothwell ALM. The nuclear receptor PPARs as important regulators of T-cell functions and autoimmune diseases. Mol Cells [Internet]. 2012;33(3):217–22. Available from: http://dx.doi.org/10.1007/s10059-012-2297-y. DOI: https://doi.org/10.1007/s10059-012-2297-y

Straus DS, Glass CK. Cyclopentenone prostaglandins: New insights on biological activities and cellular targets. Med Res Rev [Internet]. 2001;21(3):185–210. Available from: http://dx.doi.org/10.1002/med.1006. DOI: https://doi.org/10.1002/med.1006.abs

Huang Q, Ma C, Chen L, Luo D, Chen R, Liang F. Mechanistic insights into the interaction between transcription factors and epigenetic modifications and the contribution to the development of obesity. Front Endocrinol (Lausanne) [Internet]. 2018;9. Available from: http://dx.doi.org/10.3389/fendo.2018.00370. DOI: https://doi.org/10.3389/fendo.2018.00370

Le Magueresse-Battistoni B. Adipose tissue and endocrine-disrupting chemicals: Does sex matter? Int J Environ Res Public Health [Internet]. 2020;17(24):9403. Available from: http://dx.doi.org/10.3390/ijerph17249403. DOI: https://doi.org/10.3390/ijerph17249403

Nakashima K-I, Yamaguchi E, Noritake C, Mitsugi Y, Goto M, Hirai T, et al. Discovery and SAR of natural-product-inspired RXR agonists with heterodimer selectivity to PPARδ-RXR. ACS Chem Biol [Internet]. 2020;15(6):1526–34. Available from: http://dx.doi.org/10.1021/acschembio.0c00146. DOI: https://doi.org/10.1021/acschembio.0c00146

Cordeiro TN, Sibille N, Germain P, Barthe P, Boulahtouf A, Allemand F, et al. Interplay of protein disorder in retinoic acid receptor heterodimer and its corepressor regulates gene expression. Structure [Internet]. 2019;27(8):1270-1285.e6. Available from: http://dx.doi.org/10.1016/j.str.2019.05.001. DOI: https://doi.org/10.1016/j.str.2019.05.001

Schmidt J-S, Schaedlich K, Fiandanese N, Pocar P, Fischer B. Effects of Di(2-ethylhexyl) phthalate (DEHP) on female fertility and adipogenesis in C3H/N mice. Environ Health Perspect [Internet]. 2012;120(8):1123–9. Available from: http://dx.doi.org/10.1289/ehp.1104016. DOI: https://doi.org/10.1289/ehp.1104016

Loh NY, Humphreys E, Karpe F, Tomlinson JW, Noordam R, Christodoulides C. Sex hormones, adiposity, and metabolic traits in men and women: a Mendelian randomisation study. Eur J Endocrinol [Internet]. 2022;186(3):407–16. Available from: http://dx.doi.org/10.1530/eje-21-0703. DOI: https://doi.org/10.1530/EJE-21-0703

Sanchez Costa L, Rodríguez Martínez P, Medina Sala M. Determination of 23 organochlorine pesticides in animal feeds by GC-MS/MS after QuEChERS with EMR-lipid clean-up. Anal Methods [Internet]. 2018;10(43):5171–80. Available from: http://dx.doi.org/10.1039/c8ay01436a. DOI: https://doi.org/10.1039/C8AY01436A

Gokosmanoglu F, Aksoy E, Onmez A, Ergenç H, Topkaya S. Thyroid homeostasis after bariatric surgery in obese cases. Obes Surg [Internet]. 2020;30(1):274–8. Available from: http://dx.doi.org/10.1007/s11695-019-04151-5. DOI: https://doi.org/10.1007/s11695-019-04151-5

Yan H, Guo H, Cheng D, Kou R, Zhang C, Si J. Tributyltin reduces the levels of serum adiponectin and activity of AKT and induces metabolic syndrome in male mice. Environ Toxicol [Internet]. 2018;33(7):752–8. Available from: http://dx.doi.org/10.1002/tox.22562. DOI: https://doi.org/10.1002/tox.22562

Kampmann FB, Thuesen ACB, Hjort L, Bjerregaard AA, Chavarro JE, Frystyk J, et al. Increased leptin, decreased adiponectin and FGF21 concentrations in adolescent offspring of women with gestational diabetes. Eur J Endocrinol [Internet]. 2019;181(6):691–700. Available from: http://dx.doi.org/10.1530/eje-19-0658. DOI: https://doi.org/10.1530/EJE-19-0658

Imagawa M, Tsuchiya T, Nishihara T. Identification of inducible genes at the early stage of adipocyte differentiation of 3T3-L1 cells. Biochem Biophys Res Commun [Internet]. 1999;254(2):299–305. Available from: http://dx.doi.org/10.1006/bbrc.1998.9937. DOI: https://doi.org/10.1006/bbrc.1998.9937

Toubal A, Treuter E, Clément K, Venteclef N. Genomic and epigenomic regulation of adipose tissue inflammation in obesity. Trends Endocrinol Metab [Internet]. 2013;24(12):625–34. Available from: http://dx.doi.org/10.1016/j.tem.2013.09.006. DOI: https://doi.org/10.1016/j.tem.2013.09.006

Makita Y, Omura M, Ogata R. Effects of perinatal simultaneous exposure to tributyltin (TBT) andp, p′-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene) on male offspring of wistar rats. Journal of Toxicology and Environmental Health, Part A [Internet]. 2004;67(5):385–95. Available from: http://dx.doi.org/10.1080/15287390490273451. DOI: https://doi.org/10.1080/15287390490273451

Manteiga S, Lee K. Monoethylhexyl phthalate elicits an inflammatory response in adipocytes characterized by alterations in lipid and cytokine pathways. Environ Health Perspect [Internet]. 2017;125(4):615–22. Available from: http://dx.doi.org/10.1289/ehp464. DOI: https://doi.org/10.1289/EHP464

Frithioff-Bøjsøe C, Lund MAV, Lausten-Thomsen U, Hedley PL, Pedersen O, Christiansen M, et al. Leptin, adiponectin, and their ratio as markers of insulin resistance and cardiometabolic risk in childhood obesity. Pediatr Diabetes [Internet]. 2020;21(2):194–202. Available from: http://dx.doi.org/10.1111/pedi.12964. DOI: https://doi.org/10.1111/pedi.12964

Kimura R, Takahashi N, Goto T, Murota K, Kawada T. Activation of peroxisome proliferator-activated receptor-α (PPARα) in proximal intestine improves postprandial lipidemia in obese diabetic KK-Ay mice. Obes Res Clin Pract [Internet]. 2013;7(5):e353–60. Available from: http://dx.doi.org/10.1016/j.orcp.2013.05.005. DOI: https://doi.org/10.1016/j.orcp.2013.05.005

Cheng, Tan, Low, Marvalim, Lee, Tan. Exploration and development of PPAR modulators in health and disease: An update of clinical evidence. Int J Mol Sci [Internet]. 2019;20(20):5055. Available from: http://dx.doi.org/10.3390/ijms20205055. DOI: https://doi.org/10.3390/ijms20205055

Teijeiro A, Garrido A, Ferre A, Perna C, Djouder N. Inhibition of the IL-17A axis in adipocytes suppresses diet-induced obesity and metabolic disorders in mice. Nat Metab [Internet]. 2021;3(4):496–512. Available from: http://dx.doi.org/10.1038/s42255-021-00371-1. DOI: https://doi.org/10.1038/s42255-021-00371-1

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 [Internet]. 2018;159(2):779–94. Available from: http://dx.doi.org/10.1210/en.2017-00711. DOI: https://doi.org/10.1210/en.2017-00711

Arida A, Protogerou A, Kitas G, Sfikakis P. Systemic inflammatory response and atherosclerosis: The paradigm of chronic inflammatory rheumatic diseases. Int J Mol Sci [Internet]. 2018;19(7):1890. Available from: http://dx.doi.org/10.3390/ijms19071890. DOI: https://doi.org/10.3390/ijms19071890

Torras N, García-Díaz M, Fernández-Majada V, Martínez E. Mimicking epithelial tissues in three-dimensional cell culture models. Front Bioeng Biotechnol [Internet]. 2018;6. Available from: http://dx.doi.org/10.3389/fbioe.2018.00197. DOI: https://doi.org/10.3389/fbioe.2018.00197

Qiao Q, Bouwman FG, Renes J, Mariman ECM. An in vitro model for hypertrophic adipocytes: Time‐dependent adipocyte proteome and secretome changes under high glucose and high insulin conditions. J Cell Mol Med [Internet]. 2020;24(15):8662–73. Available from: http://dx.doi.org/10.1111/jcmm.15497. DOI: https://doi.org/10.1111/jcmm.15497

Niedo J, Tanimoto S, Thompson RH, Abbott RD, Berninger VW. Computerized instruction in translation strategies for students in upper elementary and middle school grades with persisting learning disabilities in written language. Learn Disabil (Pittsbg) [Internet]. 2016;21(2):14–30. Available from: http://dx.doi.org/10.18666/ldmj-2016-v21-i2-7751. DOI: https://doi.org/10.18666/LDMJ-2016-V21-I2-7751

Santos Rizzo Zuttion MS, Dias Câmara DA, Dariolli R, Takimura C, Wenceslau C, Kerkis I. In vitro heterogeneity of porcine adipose tissue-derived stem cells. Tissue Cell [Internet]. 2019;58:51–60. Available from: http://dx.doi.org/10.1016/j.tice.2019.04.001. DOI: https://doi.org/10.1016/j.tice.2019.04.001

Kunz HE, Hart CR, Gries KJ, Parvizi M, Laurenti MC, Dalla Man C, et al. Adipose tissue macrophage populations and inflammation are associated with systemic inflammation and insulin resistance in obesity. Am J Physiol Endocrinol Metab [Internet]. 2021;(ajpendo.00070.2021). Available from: http://dx.doi.org/10.1152/ajpendo.00070.2021. DOI: https://doi.org/10.1152/ajpendo.00070.2021

Micic D. Endocrine disrupting chemicals and obesity: The evolving story of obesogens. Acta Endocrinol (Buchar) [Internet]. 2021;17(4):503–8. Available from: http://dx.doi.org/10.4183/aeb.2021.503. DOI: https://doi.org/10.4183/aeb.2021.503

Murphy CS, Liaw L, Reagan MR. In vitro tissue-engineered adipose constructs for modeling disease. BMC Biomed Eng [Internet]. 2019;1(1). Available from: http://dx.doi.org/10.1186/s42490-019-0027-7. DOI: https://doi.org/10.1186/s42490-019-0027-7

Baganha F, Schipper R, Hagberg CE. Towards better models for studying human adipocytes in vitro. Adipocyte [Internet]. 2022;11(1):413–9. Available from: http://dx.doi.org/10.1080/21623945.2022.2104514. DOI: https://doi.org/10.1080/21623945.2022.2104514

Chen Y, Lee K, Kawazoe N, Yang Y, Chen G. PLGA–collagen–ECM hybrid scaffolds functionalized with biomimetic extracellular matrices secreted by mesenchymal stem cells during stepwise osteogenesis-co-adipogenesis. J Mater Chem B Mater Biol Med [Internet]. 2019;7(45):7195–206. Available from: http://dx.doi.org/10.1039/c9tb01959f. DOI: https://doi.org/10.1039/C9TB01959F

Jia G, Huang H, Niu J, Chen C, Weng J, Yu F, et al. Exploring the interconnectivity of biomimetic hierarchical porous Mg scaffolds for bone tissue engineering: Effects of pore size distribution on mechanical properties, degradation behavior and cell migration ability. J Magnes Alloy [Internet]. 2021;9(6):1954–66. Available from: http://dx.doi.org/10.1016/j.jma.2021.02.001. DOI: https://doi.org/10.1016/j.jma.2021.02.001

Wang X, Zhang X, Dai X, Wang X, Li X, Diao J, et al. Tumor-like lung cancer model based on 3D bioprinting. 3 Biotech [Internet]. 2018;8(12). Available from: http://dx.doi.org/10.1007/s13205-018-1519-1. DOI: https://doi.org/10.1007/s13205-018-1519-1

Rodrigues J, Heinrich MA, Teixeira LM, Prakash J. 3D in vitro model (R)evolution: Unveiling tumor–stroma interactions. Trends Cancer [Internet]. 2021;7(3):249–64. Available from: http://dx.doi.org/10.1016/j.trecan.2020.10.009. DOI: https://doi.org/10.1016/j.trecan.2020.10.009

Silva TM da, Oliveira FM de, Rodrigues KCP, Nobre LR, brito ml. uso de modelos animais na indução da obesidade e alterações fisiológicas / use of animal models in inducing obesity and physiological changes. Braz J Dev [Internet]. 2020;6(9):66278–86. Available from: http://dx.doi.org/10.34117/bjdv6n9-165. DOI: https://doi.org/10.34117/bjdv6n9-165

Chamorro-Garcia R, Blumberg B. Current research approaches and challenges in the obesogen field. Front Endocrinol (Lausanne) [Internet]. 2019;10. Available from: http://dx.doi.org/10.3389/fendo.2019.00167. DOI: https://doi.org/10.3389/fendo.2019.00167

Pigeot S, Klein T, Gullotta F, Dupard SJ, Garcia Garcia A, García-García A, et al. Manufacturing of human tissues as off‐the‐shelf grafts programmed to induce regeneration. Adv Mater [Internet]. 2021;33(43):2103737. Available from: http://dx.doi.org/10.1002/adma.202103737. DOI: https://doi.org/10.1002/adma.202103737

Fuchs T, Loureiro M de P, Macedo LE, Nocca D, Nedelcu M, Costa-Casagrande TA. Modelos animais na síndrome metabólica. Rev Col Bras Cir [Internet]. 2018;45(5). Available from: http://dx.doi.org/10.1590/0100-6991e-20181975. DOI: https://doi.org/10.1590/0100-6991e-20181975

Talley S, Kalinina O, Winek M, Paik W, Cannon AR, Alonzo F III, et al. A caspase-1 biosensor to monitor the progression of inflammation in vivo. J Immunol [Internet]. 2019;203(9):2497–507. Available from: http://dx.doi.org/10.4049/jimmunol.1900619. DOI: https://doi.org/10.4049/jimmunol.1900619

Ruthsatz K, Dausmann KH, Paesler K, Babos P, Sabatino NM, Peck MA, et al. Shifts in sensitivity of amphibian metamorphosis to endocrine disruption: the common frog (Rana temporaria) as a case study. Conserv Physiol [Internet]. 2020;8(1). Available from: http://dx.doi.org/10.1093/conphys/coaa100. DOI: https://doi.org/10.1093/conphys/coaa100

Checkoway H, Lees PSJ, Dell LD, Gentry PR, Mundt KA. Peak exposures in epidemiologic studies and cancer risks: Considerations for regulatory risk assessment. Risk Anal [Internet]. 2019;(risa.13294). Available from: http://dx.doi.org/10.1111/risa.13294. DOI: https://doi.org/10.1111/risa.13294

de la Torre Canny SG, Mueller O, Craciunescu CV, Blumberg B, Rawls JF. Tributyltin exposure leads to increased adiposity and reduced abundance of leptogenic bacteria in the zebrafish intestine [Internet]. bioRxiv. 2021. Available from: http://dx.doi.org/10.1101/2021.07.09.451869. DOI: https://doi.org/10.1101/2021.07.09.451869

Mittelstraß K, Waldenberger M. DNA methylation in human lipid metabolism and related diseases. Curr Opin Lipidol [Internet]. 2018;29(2):116–24. Available from: http://dx.doi.org/10.1097/mol.0000000000000491. DOI: https://doi.org/10.1097/MOL.0000000000000491

King SE, Nilsson E, Beck D, Skinner MK. Adipocyte epigenetic alterations and potential therapeutic targets in transgenerationally inherited lean and obese phenotypes following ancestral exposures. Adipocyte [Internet]. 2019;8(1):362–78. Available from: http://dx.doi.org/10.1080/21623945.2019.1693747. DOI: https://doi.org/10.1080/21623945.2019.1693747

Meruvu S, Zhang J, Choudhury M. Butyl benzyl phthalate promotes adipogenesis in 3T3-L1 cells via the miRNA-34a-5p signaling pathway in the absence of exogenous adipogenic stimuli. Chem Res Toxicol [Internet]. 2021;34(11):2251–60. Available from: http://dx.doi.org/10.1021/acs.chemrestox.1c00115. DOI: https://doi.org/10.1021/acs.chemrestox.1c00115

Ye C, Sutter BM, Wang Y, Kuang Z, Zhao X, Yu Y, et al. Demethylation of the protein phosphatase PP2A promotes demethylation of histones to enable their function as a methyl group sink. Mol Cell [Internet]. 2019;73(6):1115-1126.e6. Available from: http://dx.doi.org/10.1016/j.molcel.2019.01.012. DOI: https://doi.org/10.1016/j.molcel.2019.01.012

Jarmasz JS, Stirton H, Basalah D, Davie JR, Clarren SK, Astley SJ, et al. Global DNA methylation and histone posttranslational modifications in human and nonhuman primate brain in association with prenatal alcohol exposure. Alcohol Clin Exp Res [Internet]. 2019; Available from: http://dx.doi.org/10.1111/acer.14052. DOI: https://doi.org/10.1111/acer.14052

Song X, Zhou X, Yang F, Liang H, Wang Z, Li R, et al. Association between prenatal bisphenol a exposure and promoter hypermethylation of CAPS2, TNFRSF25, and HKR1 genes in cord blood. Environ Res [Internet]. 2020;190(109996):109996. Available from: http://dx.doi.org/10.1016/j.envres.2020.109996. DOI: https://doi.org/10.1016/j.envres.2020.109996

Sun L, Lizneva D, Ji Y, Colaianni G, Hadelia E, Gumerova A, et al. Oxytocin regulates body composition. Proc Natl Acad Sci U S A [Internet]. 2019;116(52):26808–15. Available from: http://dx.doi.org/10.1073/pnas.1913611116. DOI: https://doi.org/10.1073/pnas.1913611116

Fujita Y, Kouda K, Nakamura H, Iki M. Relationship between maternal pre-pregnancy weight and offspring weight strengthens as children develop: A population-based retrospective cohort study. J Epidemiol [Internet]. 2018;28(12):498–502. Available from: http://dx.doi.org/10.2188/jea.je20170137. DOI: https://doi.org/10.2188/jea.JE20170137

Wang D, Yan S, Yan J, Teng M, Meng Z, Li R, et al. Effects of triphenyl phosphate exposure during fetal development on obesity and metabolic dysfunctions in adult mice: Impaired lipid metabolism and intestinal dysbiosis. Environ Pollut [Internet]. 2019;246:630–8. Available from: http://dx.doi.org/10.1016/j.envpol.2018.12.053. DOI: https://doi.org/10.1016/j.envpol.2018.12.053

Yan S, Wang D, Teng M, Meng Z, Yan J, Li R, et al. Perinatal exposure to low-dose decabromodiphenyl ethane increased the risk of obesity in male mice offspring. Environ Pollut [Internet]. 2018;243(Pt A):553–62. Available from: http://dx.doi.org/10.1016/j.envpol.2018.08.082. DOI: https://doi.org/10.1016/j.envpol.2018.08.082

Guo J, Zhang J, Wu C, Xiao H, Lv S, Lu D, et al. Urinary bisphenol A concentrations and adiposity measures at age 7 years in a prospective birth cohort. Chemosphere [Internet]. 2020;251(126340):126340. Available from: http://dx.doi.org/10.1016/j.chemosphere.2020.126340. DOI: https://doi.org/10.1016/j.chemosphere.2020.126340

Choi R-Y, Lee H-I, Ham JR, Yee S-T, Kang K-Y, Lee M-K. Heshouwu (Polygonum multiflorum Thunb.) ethanol extract suppresses pre-adipocytes differentiation in 3T3-L1 cells and adiposity in obese mice. Biomed Pharmacother [Internet]. 2018;106:355–62. Available from: http://dx.doi.org/10.1016/j.biopha.2018.06.140. DOI: https://doi.org/10.1016/j.biopha.2018.06.140

Summerfield M, Zhou Y, Zhou T, Wu C, Alpini G, Zhang KK, et al. A long-term maternal diet transition from high-fat diet to normal fat diet during pre-pregnancy avoids adipose tissue inflammation in next generation. PLoS One [Internet]. 2018;13(12):e0209053. Available from: http://dx.doi.org/10.1371/journal.pone.0209053. DOI: https://doi.org/10.1371/journal.pone.0209053

Hölttä-Vuori M, Salo VTV, Nyberg L, Brackmann C, Enejder A, Panula P, et al. Zebrafish: gaining popularity in lipid research. Biochem J [Internet]. 2010;429(2):235–42. Available from: http://dx.doi.org/10.1042/bj20100293. DOI: https://doi.org/10.1042/BJ20100293

Zoeller RT, Brown TR, Doan LL, Gore AC, Skakkebaek NE, Soto AM, et al. Endocrine-disrupting chemicals and public health protection: A statement of principles from the endocrine society. Endocrinology [Internet]. 2012;153(9):4097–110. Available from: http://dx.doi.org/10.1210/en.2012-1422. DOI: https://doi.org/10.1210/en.2012-1422

Birnbaum LS. State of the science of endocrine disruptors. Environ Health Perspect [Internet]. 2013;121(4). Available from: http://dx.doi.org/10.1289/ehp.1306695. DOI: https://doi.org/10.1289/ehp.1306695

Gu J, Su T, Chen Y, Zhang Q-Y, Ding X. Expression of biotransformation enzymes in human fetal olfactory mucosa: Potential roles in developmental toxicity. Toxicol Appl Pharmacol [Internet]. 2000;165(2):158–62. Available from: http://dx.doi.org/10.1006/taap.2000.8923. DOI: https://doi.org/10.1006/taap.2000.8923

Pine CJ. Anxiety and eating behavior in obese and nonobese American Indians and White Americans. J Pers Soc Psychol [Internet]. 1985;49(3):774–80. Available from: http://dx.doi.org/10.1037/0022-3514.49.3.774. DOI: https://doi.org/10.1037//0022-3514.49.3.774

Andrich DE, Melbouci L, Ou Y, Leduc-Gaudet J-P, Chabot F, Lalonde F, et al. Altered feeding behaviors and adiposity precede observable weight gain in young rats submitted to a short-term high-fat diet. J Nutr Metab [Internet]. 2018;2018:1–10. Available from: http://dx.doi.org/10.1155/2018/1498150. DOI: https://doi.org/10.1155/2018/1498150

Rasdi Z, Kamaludin R, Ab. Rahim S, Syed Ahmad Fuad SB, Othman MHD, Siran R, et al. The impacts of intrauterine Bisphenol A exposure on pregnancy and expression of miRNAs related to heart development and diseases in animal model. Sci Rep [Internet]. 2020;10(1). Available from: http://dx.doi.org/10.1038/s41598-020-62420-1. DOI: https://doi.org/10.1038/s41598-020-62420-1

Tian S, Lei P, Zhang J, Sun Y, Li B, Shan Y. Sulforaphane balances ca 2+ homeostasis injured by excessive fat via mitochondria‐associated membrane (MAM). Mol Nutr Food Res [Internet]. 2021;65(14):2001076. Available from: http://dx.doi.org/10.1002/mnfr.202001076102. DOI: https://doi.org/10.1002/mnfr.202001076

Robles-Aguilera V, Gálvez-Ontiveros Y, Rodrigo L, Salcedo-Bellido I, Aguilera M, Zafra-Gómez A, et al. Factors associated with exposure to dietary bisphenols in adolescents. Nutrients [Internet]. 2021;13(5):1553. Available from: http://dx.doi.org/10.3390/nu13051553. DOI: https://doi.org/10.3390/nu13051553

Griffin, M. D., Pereira, S. R., DeBari, M. K., & Abbott, R. D. (2020). Mechanisms of action, chemical characteristics, and model systems of obesogens. BMC Biomedical Engineering, 2, 6. https://doi.org/10.1186/s42490-020-00040-6. DOI: https://doi.org/10.1186/s42490-020-00040-6