The endocrine disrupting chemicals and obesity prevention  - Scoping review

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The aim of this review article is to gather current knowledge about EDCs and obesity in humans. We conducted an electronic literature search using PubMed platform for studies published between y. 2013-2023 on EDCs and obesity. A total of 12 studies met our inclusion criteria focusing on more prominent EDCs such as bisphenols, parabens, triclosan, and phthalates, and their association with obesity. A few experimental studies have been performed on association of obesity and EDCs in humans. Obesity was mostly related to EDCs such as bisphenols and phthalates, while less is known about the impact of parabens and triclosan. Series of negative physiological effects involving obesogenic, diabetogenic, and inflammatory mechanisms, epigenetic and microbiota modulations were related to prolonged EDCs exposure. More profound research of obesity with specific design regarding its role, genetic background for diabetes-related features, cardiometabolic risks and anthropometrical exceeds are needed to illuminate the effect of EDCs exposure on human populations in different environments. bisphenols parabens triclosan phthalates obesity Figures Figure 1 Figure 2 Figure 3 Introduction The excess body weight limit human performance, especially in ergonomically demanding occupations. For ergonomically demanding professions it is therefore important to ensure safety and preventive measures at work. Both, the excess weight, and the environmental excesses of different contaminants are accompanied by different health problems (Amato et al., 2021; Runkel et al., 2021; Srnovršnik et al., 2023; Tkalec et al., 2021; Woodruff et al., 2023). The environmental chemicals interrupting endocrine system known as endocrine disrupting chemicals (EDCs) are associated with reproductive complications, hormone-sensitive cancers, problems with thyroid function, changes of neuroendocrine systems and microbiota, diabetes, and obesity (Gore et al., 2015). Much research in recent years has focused on understanding plausible mechanisms underlying actions of endocrine disrupting chemicals (EDCs) and how human and animal exposures, especially during development, may lay the foundations for disease later in life. Environmental stressors such as EDCs are classified as potential obesogens, substances that cause obesity, but more profound conclusions based on experimental human studies are needed (Haverinen et al., 2021). General objective of the minimization of EDCs exposure and body burden is a pertinent central goal of the European regulation. The major current focus of EDCs research is epigenetics, microbiome, safe chemistry, dose-response functions of EDCs and their effects, and metabolism. Definitions of substances with endocrine-disrupting activities are now present in the EU regulation in the context of plant protection products and biocides. While threshold values of widely present pseudo-persistent chemicals are known, the specific test for other EDCs identifications and EU regulations are required (EP, 2019). The recent findings suggest that EDCs, especially bisphenol A (BPA), during all life stages correlates with increased body weight and/or body mass index, adipogenesis, adipose tissue inflammation, lipids, and glucose dysregulation, thus contributing to the weight gain and pathophysiology of obesity (Kumar et al., 2020; Darbre, 2017; Naomi et al., 2022; Legeay & Faure, 2017). Studies demonstrated the EDCs can bind to different hormone receptors (Figure 1), mostly those for estrogens, with specific agonistic or antagonistic effects and responses (De Coster & van Larebeke, 2012; Kim & Lee, 2017). The estrogens preserve the integrity of energy homeostasis at central and peripheral levels via nuclear and extranuclear pathways in both females and males (Mahboobifard et al., 2022). Moreover, some studies confirmed that BPA exerts its disrupting effects on the classical nuclear receptors such as estrogen receptors alpha and beta (ERa and ERb), non-classical membrane estrogen receptor (ncmER), estrogen-related receptor gamma (ERRg), G protein- coupled receptor 30 (GPR30), and the aryl hydrocarbon receptor (AhR) (Alonso-Magdalena et al., 2012). Through these interactions, BPA is thought to be involved in the onset of metabolic dysfunction. We need to take a closer look at EDCs to understand their impact on health and obesity in humans. The aim of this review was to summarize the current evidence regarding environmental EDCs – bisphenols – bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS), parabens, phthalates, and triclosan, and their association with obesity (Figure 2). This review article focuses on the following endocrine disrupting chemicals: Bisphenols Bisphenol A (BPA; 4,4′-(Propane-2,2-diyl) diphenol; C 15 H 16 O 2 ) is a synthetic chemical compound which was developed in the 1890s and its effect on estrogen activity was recognized in 1930s (Richter et al., 2007). BPA has been used in many consumer products including plastics (as a polymer); polycarbonate plastic (PVC), food packaging, dental sealants, and thermal receipts. Humans are exposed to BPA through their diet, inhalation of household dust, and dermal exposure (Wetherill et al., 2007, Carwile et al., 2009). Moreover, due to health concerns BPA was largely replaced by bisphenol F (BPF; 4,4′-Methylenediphenol; C 13 H 12 O 2 ) and bisphenol S (BPS; 4,4′-Sulfonyldiphenol; C 12 H 10 O 4 S) , which resulted in increased production of BPF and BPS over the last few decades (Fürhacker et al., 2000). However, it was found that both BPS and BPF are toxic and have the potential to interrupt metabolic action like BPA with some exceeding that of BPA (Vinas & Watson, 2013). Parabens Parabens (PBs), chemically a series of parahydroxybenzoates or esters of parahydroxybenzoic acid (also known as 4-hydroxybenzoic acid) include a group of chemicals which are used as preservatives in the food, cosmetic and pharmaceutical industries (Cashman & Warshaw, 2005). Their estrogenic effects were associated with the endocrine organs and other tissues, including adipose tissue. Several of these chemicals are known to cause obesogenic effects. In some experimental studies, it was found that there are some important associations between methylparaben exposure and adipsin, affecting energy balance in the body and metabolic health thus indicating its obesogenic potential (Kolatorova et al., 2018). In human biomonitoring PBs levels were associated with canned food and use of personal care products such as makeup and skin products (Sanchis et al., 2019; Tkalec et al., 2021). Triclosan Triclosan (TCS; 5-Chloro-2-(2,4-dichlorophenoxy) phenol; C 12 H 7 Cl 3 O 2 ) developed in 1966 ( Boyce & Pittet, 2002) is usually found in personal care products as an antibacterial agent. In animal studies, TCS exposure was associated with androgenic and thyroid disturbance, contact dermatitis, and skin irritation ( Thompson et al., 2005). Beside the estrogenic and androgenic effects in mammals, some studies suggest the potential of TCS to trigger antibiotic resistance (Goodman et al., 2018; Runkel et al., 2022). Phthalates Phthalates, esters of phthalic acid (C 6 H 4 (CO 2 H) 2 ), are chemicals which are used to improve the utility of plastics and personal care products in daily life (Kumari & Pulimi, 2023). A high-molecular-weight phthalates can enable flexibility of plastics, and are used as components in toys, building materials, medical devices, and paints. Meanwhile, low-molecular-weight phthalates are usually used as components of personal care products and cosmetics such as shampoos, lotions, nail care products, and other personal hygiene products. In general, phthalates are well-known EDCs with anti-androgenic effects (Lee et al., 2022). Materials and methods This scoping review was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA, Figure 3) guideline (Tricco et al., 2018). We conducted an electronic literature search utilizing the National Library of Medicine (PubMed) database. The following medical subject heading (MESH) keywords were used to search for studies reporting on the role of environmental endocrine disruptors in the occurrence of obesity: ‘'endocrine disruptors” OR “endocrine disrupting chemicals” AND “obesity”. Selected Literature The focus of the literature selection was to investigate the effects of pseudo-persistent EDCs such as BPA, parabens, phthalates and triclosan in studies. The database was searched for studies published in a decade from May 2013 until December 2023. Included studies were experimental studies (randomized control studies, case-control studies, cross-sectional studies, pilot studies or cohort studies), and meta-analyses. Studies published in languages other than English, were excluded from this review. We also performed a hand search of the reference lists of full-text articles that met our criteria in the primary literature search. All manuscripts and abstracts were independently reviewed by investigators for possible study inclusion regarding their subject and quality. The selected articles were read in full to confirm eligibility and to extract data. Studies and manuscripts were confirmed by all researchers included. Data Extraction After primary search, we identified 245 potentially eligiable citations. Based on our inclusion criteria, we selected 12 studies for initial screening. By reviewing the references lists of selected studies, we revealed no additional potentialy eligiable citations. Studies that met our inclusion criteria identified possibble association of exposure to main EDCs (bisphenols, parabens, triclosans and phthalates) with obesity or overweight (Table 1). Figure 3 presents a PRISMA flow diagram of the association of EDCs with obesity. From included studies, the following information was extracted for detailed evaluation: characteristics of the included studies (authors and year of publication), study design characteristics (sample type, sample size), methods (analyses, exposure), type of outcome assessment (type of endocrine disruptor) and the main findings (conclusions). Results Studies identifying possible association of obesity with the exposure to endocrine disrupting chemicals (EDCs). The data on experimental studies, meta-analyses and systematic review studies are presented in Table 1. Literature Identification The possible effects of endocrine disrupting chemicals on obesity in humans described in experimental studies and meta-analysis are summarized in Table 1. Table 1. The possible effects of endocrine disrupting chemicals on obesity in humans. First author, year Study design, Sample size Analysis, Exposure Outcome assessment Conclusions Dirinck et al., 2016 Cohort study, 184 metabolically unhealthy obese (MUO) and metabolically healthy obese (MHO) males (53) and females (131) 6 and 12 months of weight loss protocol (lifestyle counseling or bariatric surgery) Serum EDCs (PCB) levels, metabolic health data (body weight, blood pressure, lipids, inflammation, glucose metabolism) Higher serum concentrations of PCBs in MUO compared to MHO. Concentration of PCBs does not differ after weight loss. Brown et al., 2019 Observational study, 27 obese adults with laparoscopic bariatric surgery Analyses of EDCs during weight loss Biological measurements of different EDCs (venous blood, urine) EDCs (POPs) levels increased as weight loss occurred. Liu et al., 2018 Prospective study, Randomized clinical trial, 621 overweight and obese adults Energy restricted diets on weight changes (4 different macronutrient diet protocols) EDCs (PFASs), biological samples (glucose, lipids, thyroid hormones, leptin), RMR Higher baseline PFASs levels were associated with greater decrease in RMR. Guo et al., 2016 Clinical Trial, Pilot Study, 15 female adults: 8 obese/overweight and 7 with normal weight 2 months of antioxidant intervention Biological samples of EDCs (blood PCBs) Vitamin C s (1000 mg/day) decreases body burden of POPs . Menale et al., 2015 In vitro exposure of human adipocytes to BPA, 8 non-obese prepubescent boys Evaluated doses of BPA that interfere with estrogen function in metabolism EDCs (BPA), biological samples (adipose cells from subcutaneous tissue) BPA in mature adipocytes lead to molecular changes promoting metabolic disorders. Predieri et al., 2020 Meta-analysis including experimental/epidemiological animal and human studies (n=65) Predispositions of T1D development and EDCs exposure Exposure to EDCs in patients with T1D Further studies with advanced biological techniques are needed to clarify risk factors of different mechanisms of T1D. Ribeiro et al., 2020 Systematic Review, Meta-analysis including 73 studies on (mostly cross-sectional design) Addressing an association of EDCs and anthropometric measures of obesity/body fat EDCs (BPA, phthalates, parabens) and obesity level or body fat BPA and phthalates associated with general and abdominal obesity. Lee et al., 2022 Systematic Review, Meta-analysis including 22 longitudinal and 17 cross-sectional studies Analyses of prenatal and postnatal EDCs exposure association with growth disturbances. EDCs (phthalate) exposure and body mass index (BMI) and fat mass Prenatal phthalate exposure associated with low BMI, but not with body fat mass. Wassenaar & Legler, 2017 Systematic Review, Meta-analysis including 31 animal studies on body and fat weight Analyses of obesogenic effects of phthalates in rodents EDCs (phthalates), obesity data (body weight, fat weight, triglycerides, free fatty acids, leptin) Early life exposure to phthalates is potentially associated with increased adiposity in rodents. Hwang et al., 2018 Meta-analysis including 16 studies (12 cross-sectional, 2 case-control, 1 prospective study) Risk evaluation of T2DM and BPA Urine and serum EDCs (BPA), T2DM BPA exposure positively associated with T2DM risk in humans. Mendes et al., 2021 Systematic Review, Meta-analysis including 31 studies (mostly cross-sectional approach) Association analyses of EDCs, adiposity and diabetes EDCs (chlordane) levels, obesity, diabetes Data did not allow to reach clear conclusion regarding the association with adiposity. Golestanzadeh et al., 2019 Meta-analysis including 99 studies (17 cohort, 15 cross-sectional, 3 case-control studies) Association analyses between EDCs and cardiometabolic risk factors EDCs (phthalates), obesity level in children and adolescents A positive association between phthalate and some cardiometabolic risk factors. Legend: PCBs-polychlorinated biphenyls; MUO-metabolically unhealthy obese; MHO-metabolically healthy obese; POPs-persistent organic pollutants; EDCs-endocrine disrupting chemicals; PFAS- Perfluoroalkyl substances; RMR-resting metabolic rate; T1D- type 1 diabetes; T2DM-Type 2 diabetes mellitus; BMI- body mass index. The main conclusions of 12 reviewed studies indicate that some obesity indications such as adipocytes changes, fat mass and RMR might be related with EDCs exposure (Dirinck et al., 2016; Brown et al., 2019; Liu et al., 2018; Menale et al., 2015; Ribeiro et al., 2020; Lee et al., 2022; Wassenaar & Legler, 2017; Hwang et al., 2018, Golestanzadeh et al., 2019) while some data did not allow to reach clear conclusions regarding EDCs with adiposity or cardiometabolic risk factors (Predieri et al., 2020; Mendes et al., 2021). In addition, researchers also suggested that antioxidant intervention might decrease the negative effects of studied EDCs (Guo et al., 2016). Discussion We have reviewed experimental studies, meta-analyses, and systematic reviews regarding a general association between obesity and exposure to widely present environmental endocrine-disrupting chemicals (EDCs). Environmental stressors such as EDCs with broad implications, including the potential development of health symptoms, diseases and performance limitations in pilots should not be neglected. This review argues the importance of environmental exposure control as a tool to promote preventive health behaviors in pilots. Research findings of 12 studies were included and they suggest that EDCs may play a role in the current epidemiology of obesity. Obesity and overweight identification, treatment, and prevention present major public health challenges in multiple perspectives globally (WHO, 2021 ). The physiopathology and clinical impacts of excess body fat (BF) are incompletely understood, and there are many difficulties in developing safe and effective long-term therapeutic strategies (Heymsfield & Wadden, 2017 ). Specifically, a higher blood levels of EDCs in metabolically unhealthy obese persons compared to metabolically healthy obese persons were demonstrated in experimental studies. Interestingly, the weight loss protocols did not change the EDCs levels in biological samples (Dirinck et al., 2016 ), or the level of EDCs even increased as weight loss occurred (Brown et al., 2019 ). Moreover, higher level of EDCs was associated with greater weight regain explained with greater decrease in resting metabolic rate (Liu et al., 2018 ). Researchers evaluating environmentally relevant doses of EDCs that interfere with estrogen function in metabolism found some molecular changes which promote metabolic disorders (Menale et al., 2015 ). In addition, potential vitamin supplementations were analyzed to reduce toxic effects of EDCs, which needs to be further investigated (Guo et al., 2016 ). Conclusions of meta-analyses show EDCs as obesogenic (Riberiro et al., 2020, Wasseraar & Legler, 2018) and suggest the association of EDCs with type 2 diabetes mellitus (Hwang et al., 2018 ) and cardio-vascular risk (Dirinck et al., 2016 , Golestanzadeh et al., 2019 ). In addition, the EDCs were associated with generalize and abdominal obesity (Ribeiro, 2020). Trans-generational inheritance and bioaccumulation of EDCs are clear obstacles for new research evidence (Laureta et al., 2019). Prenatal life exposure to EDCs was associated with low body mass index (BMI) (Lee et al., 2022 ) and increased level of fat mass in children (Wassenaar & Legler, 2017 ). More studies are warranted to elucidate the mechanisms underlying the link between EDCs exposure and metabolic health (Liu et al., 2018 ). EDCs are lipophilic environmental toxicants and as such bio-accumulate in adipose tissues thus presenting increasing health hazards in individuals with excess body weight (Brown et al., 2019 ). Weight loss was related to the release and redistribution of organic pollutants to other lipid-rich organs such as the brain, kidney, and liver, which needs further investigations. It was suggested that even weight control interventions should be considered to limit organ exposure to pollutants when weight loss protocols are planned. Moreover, in diet induced weight-loss, higher baseline plasma EDCs concentrations were significantly associated with greater weight regain, especially in women, accompanied by a slower regression of resting metabolic rate (Liu et al., 2018 ). It is necessary to understand the complexity of the mechanisms which are involved in differentiation of fat cells and the influence of EDCs in the adipogenesis and the etiology of obesity (González-Casanova et al., 2020 ). The findings indicate a significant association between exposure to BPA and obesity in adults but are insufficient to support that EDCs cause obesity “per se” in humans due to the cross-sectional design of most included studies (Ribeiro et al., 2020 ). González-Casanova et al. ( 2020 ) reported that EDCs can alter lipid metabolism, promote fat accumulation, and interfere with processes such as adipogenesis through the immunomodulation effects and other mechanisms of action such as microbiota and epigenetics. Findings on animal’s immune and inflammatory responses support the idea that further investigations are needed in human, to better understand the health consequences of EDCs exposure. However, humans may be exposed to more EDCs at the same time and exposure varies over time, what makes it impossible to evaluate theirs potential synergistic or antagonistic effects. As well, it is important that EDCs have a very short urinary elimination half-life in the human body and it may be necessary to consider if a single urine or blood sample is representative of the overall exposure of an individual, including the subjective level of daily environmental exposure. EDCs act via various hormone receptors through a variety of known and unknown mechanisms including epigenetic modifications. They differ from classic toxins in several ways such a slow-dose effect (time after exposure), non-monotonic dose and trans-generational effects. Specifically, the results of included studies suggested that BPA is associated with obesity and may negatively affect the metabolic functions in various ways. Some epidemiological studies which were using data from the National Health and Nutrition Examination Survey (NHANES) reported that higher urine BPA concentrations tend to be correlated with greater obesity risk and waist circumference (Shankar et al., 2012 ; Bhandari et al., 2013 ). Researchers confirmed a significant relationship between BPA and childhood obesity (Kim & Lee, 2019). Menale at al. (2015) described the role of BPA in modulating canonical endocrine function, which regulates metabolism during childhood. It was reported that BPA at environmental doses acts in mature adipocytes by modulating gene expression, which leads to molecular changes that promote metabolic disorders in children. The persistence of BPA in the environment and in the human adipose tissue might be an important risk factor and a strong argument for further research of the obesity development (Menale et al., 2015 ). Wassenaar & Legler ( 2017 ) reported that early life exposure of animals to phthalates is associated with increased fat weight, while non-significant negative association was associated with body weight. On the other hand, studies on the association between exposure to phthalates in childhood and obesity were inconsistent. Specifically, prenatal phthalate exposure may disturb the normal growth of children by decreased BMI rather than causing obesity, as hypothesized by previous studies (Lee et al., 2022 ). Moreover, it was recently discovered that BPA and phthalates are cardiovascular disruptors and BPA by itself could have a direct relationship with systemic inflammation regardless of obesity or insulin resistance. Parabens were related with obesogenic potential affecting energy balance and metabolic health (Kolatorova et al., 2018 ). While contradictory results were obtained regarding triclosan and obesity, one of recent animal studies emphasized the underlying toxic obesogenic mechanism of triclosan which is based on gut-brain axis (Wang et al., 2022 ). However, the relationship between triclosan and parabens with obesity remains unclear and inconclusive, and further research is needed. Increased exposure to EDCs could pose long-term health risk effects. EDCs are ubiquitous contaminants with a broad spectrum of effects. The chemicals such as BPA, parabens, triclosan and phthalates are common environmental pollutants which are incriminated for metabolic as well as a reproductive disorders. Therefore, most published literature concerning EDCs and obesity is limited mostly to diabetes and BPA. Therefore, human research combining biomonitoring, analyses of biological samples, and structured questionnaire of life-quality, food and physical activity to evaluate the association between lifestyle variables potentially related to EDCs could present one of the possible designs of more profound strategy to understand the association of EDCs and obesity. However, the qualitative similarity of most data indicate that EDCs are related with obesity through various physiological pathways that may also lead to weight gain. Therefore, the conclusions thus might serve as an awareness to avoid the exposure of EDCs. This is particularly important in the current worldwide scenario of ongoing exposure of children and adults to EDCs, not only to chemicals which are still used for a wide range of purposes but also to compounds that were banned in many countries but have persistent and ubiquitous occurrence in the environment. To better illuminate the environmental triggers of obesity, further studies on larger populations are needed. In this review, we summarized the knowledge on the association of EDCs such as BPA, parabens, triclosan and phthalates with obesity in the last 10 years. Revealed studies, methodologically heterogenic, have reported a potential association between prolonged exposure to EDCs and obesity mainly through diabetes and metabolic disorders, while exact mechanisms remain scarce. However, main findings of this review need to be interpreted with caution due to used methodology investigating EDCs and obesity, selected database, and a small number of existing experimental studies. Recent research indicates that there is a specific need to combine human biomonitoring with other investigating methods to evaluate quality of life including exposure to environmental triggers such as plastic, and personal hygiene products of the observed population. More studies on molecular effects are needed to understand an association of EDCs with metabolic diseases, particularly human obesity. The exposure of environmental triggers and possible associations with human performance and disease prevention should not be neglected. Limitations Our scoping review has some limitations. Our literature search was limited to a single database and to publications available entirely in the English language, potentially excluding valuable research conducted in other languages and from other databases. Lastly, our results are only up to date as of December 2023, and any subsequent studies beyond this timeframe are not incorporated into our review. Conclusion Regardless of some inconsistences in the findings across summarized studies, involuntary exposure to EDCs might be related with obesity development. Further studies including multicentric studies are needed to delineate exact mechanisms through which EDC exposure causes obesity so that efficient preventative measures could be implemented. The lack of public knowledge about the effects of EDCs on human health is worrying, which should induce health care providers to inform especially specific health population or ergonomically demanding populations to avoid the excess body weight and possible EDC exposure thus empowering them to make healthy choices. Declarations Author contributions All authors have contributed to the article, read manuscript, agreed with the content, and approved the submitted version. Authors confirm that the manuscript is original and has not been published in a journal and is not currently under consideration by another journal. MA collected the data for paper, coordinated and contributed at all stages of the review and critically reviewed the final review. TK contributed to the writing of the review and contributed to the strategy development and in all stages of the review. IVK contributed to the writing of the paper and participated in all stages of data collection. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Availability of data and materials All data gathered during this study are included in the published article. Competing interests The authors declare no competing interests. Consent for publication Not applicable. References Alonso-Magdalena P, Ropero AB, Soriano S, García-Arévalo M, Ripoll C, et. al. Bisphenol-A acts as a potent estrogen via non-classical estrogen triggered pathways. Mol Cell Endocrinol, 2012; 355(2): 201-7. 10.1016/j.mce.2011.12.012 Amato AA, Wheeler HB, Blumberg B. 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BMJ Open. 2020; 10(6):e033509. 10.1136/bmjopen-2019-033509 Richter CA, Birnbaum LS, Farabollini F, Newbold RR, Rubin BS, et al. In vivo effects of bisphenol A in laboratory rodent studies. Reprod Toxicol. 2007; 24(2):199-224. 10.1016/j.reprotox.2007.06.004 Runkel AA, Mazej D, Snoj Tratnik J, Tkalec Ž, Kosjek T, et al. Exposure of men and lactating women to environmental phenols, phthalates, and DINCH. Chemosphere. 2022; 286(3):131858. 10.1016/j.chemosphere.2021.131858 Sanchis Y, Coscollà C, Yusà V. Analysis of four parabens and bisphenols A, F, S in urine, using dilute and shoot and liquid chromatography coupled to mass spectrometry. Talanta. 2019; 202:42-50. 10.1016/j.talanta.2019.04.048 Shankar A, Teppala S, Sabanayagam C. Bisphenol A and peripheral arterial disease: results from the NHANES. Environ Health Perspect. 2012; 120(9):1297-300. 10.1289/ehp.1104114 Srnovršnik T, Virant-Klun I, Pinter B. Polycystic Ovary Syndrome and Endocrine Disruptors (Bisphenols, Parabens, and Triclosan)-A Systematic Review. Life (Basel). 2023; 13(1):138. 10.3390/life13010138 Tkalec Ž, Kosjek T, Snoj Tratnik J, Stajnko A, Runkel AA, et al. Exposure of Slovenian children and adolescents to bisphenols, parabens and triclosan: Urinary levels, exposure patterns, determinants of exposure and susceptibility. Environ Int. 2021; 146: 106172. 10.1016/j.envint.2020.106172 Thompson A, Griffin P, Stuetz R, Cartmell E. The Fate and Removal of Triclosan during Wastewater Treatment. Water Environment Research. 2005; 77(1):63–67. 10.2175/106143005X41636 Tricco AC, Lillie E, Zarin W, O'Brien KK, Colquhoun H, Levac D, Moher D, Peters MDJ, Horsley T, Weeks L, Hempel S, Akl EA, Chang C, McGowan J, Stewart L, Hartling L, Aldcroft A, Wilson MG, Garritty C, Lewin S, Godfrey CM, Macdonald MT, Langlois EV, Soares-Weiser K, Moriarty J, Clifford T, Tunçalp Ö, Straus SE. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med. 2018; 169(7): 467-473. doi: 10.7326/M18-0850. Epub 2018 Sep 4. PMID: 30178033. Viñas R, Watson CS. Bisphenol S disrupts estradiol-induced nongenomic signaling in a rat pituitary cell line: effects on cell functions. Environ Health Perspect. 2013; 121(3):352-8. 10.1289/ehp.1205826 Wang Y, Song J, Wang X, Qian Q, Wang H. Study on the toxic-mechanism of triclosan chronic exposure to zebrafish (Danio rerio) based on gut-brain axis. Sci Total Environ. 2022; 2022844:156936. 10.1016/j.scitotenv.2022.156936 Wassenaar PNH, Legler J. Systematic review and meta-analysis of early life exposure to di(2-ethylhexyl) phthalate and obesity related outcomes in rodents. Chemosphere. 2017; 188:174-181. 10.1016/j.chemosphere.2017.08.165 Wetherill YB, Akingbemi BT, Kanno J, McLachlan JA, Nadal A, et al. In vitro molecular mechanisms of bisphenol A action. Reprod Toxicol. 2007; 24(2):178-98. 10.1016/j.reprotox.2007.05.010 Woodruff TJ, Charlesworth A, Zlatnik MG, Pandipati S, DeNicola N, et al. Code OB: We need urgent action on climate change and toxic chemicals. Int J Gynaecol Obstet, 2023; 160(2):363-365. 10.1002/ijgo.14566 WHO, 2021. Obesity and overweight. 2021-2023. World Health Organization; [accessed 2023, Oct 2]. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight/. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 03 Sep, 2024 Read the published version in Journal of Health, Population and Nutrition → Version 1 posted Editorial decision: Revision requested 26 Apr, 2024 Reviews received at journal 17 Apr, 2024 Reviews received at journal 11 Apr, 2024 Reviewers agreed at journal 11 Apr, 2024 Reviewers agreed at journal 10 Apr, 2024 Reviewers agreed at journal 10 Apr, 2024 Reviewers invited by journal 10 Apr, 2024 Editor assigned by journal 09 Apr, 2024 Submission checks completed at journal 04 Apr, 2024 First submitted to journal 03 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4212370","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":290148220,"identity":"f72e465d-ef94-4053-b74a-7f3ae72b49f5","order_by":0,"name":"Mojca Amon","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYHCCBCjNfJiBoYANSBOvhS2ZgcGAOC0wwGMM1EKEOt32hocffjDYRfNL93w2+GHAxyDfTkCL2ZkDyZI9DMm5M+ec3ZzYA3SYwWFCWm4kpDHwMDDnbriRu/kwyC8GhPwC0sL4h6EeqCXnMViLfDMRWph5GA6DtDAng0OMoMOAfpGWMTieO3NGmrEh0C88hP1yvCfx45uK6tx+ieTHEj8qjsnJ9x8goIeBJwE5Oo7xEFIPBOwohtYQoWMUjIJRMApGGgAAbkk9lVFf1Y8AAAAASUVORK5CYII=","orcid":"","institution":"University Medical Centre Ljubljana","correspondingAuthor":true,"prefix":"","firstName":"Mojca","middleName":"","lastName":"Amon","suffix":""},{"id":290148221,"identity":"cf1e1dd7-6c99-4566-b3d8-d08636c918fb","order_by":1,"name":"Tina Kek","email":"","orcid":"","institution":"University Medical Centre Ljubljana","correspondingAuthor":false,"prefix":"","firstName":"Tina","middleName":"","lastName":"Kek","suffix":""},{"id":290148222,"identity":"647f174d-56a7-4c23-b545-e4af8c8760b1","order_by":2,"name":"Irma Virant Klun","email":"","orcid":"","institution":"University Medical Centre Ljubljana","correspondingAuthor":false,"prefix":"","firstName":"Irma","middleName":"Virant","lastName":"Klun","suffix":""}],"badges":[],"createdAt":"2024-04-03 11:27:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4212370/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4212370/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s41043-024-00627-y","type":"published","date":"2024-09-03T16:05:49+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":54572978,"identity":"9112d1ac-590c-49f8-a627-791eb9583bfe","added_by":"auto","created_at":"2024-04-12 13:12:00","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":154930,"visible":true,"origin":"","legend":"\u003cp\u003eEDCs have an ability to bind to different hormone receptors.\u003c/p\u003e","description":"","filename":"EDCsreceptors.JHPN.png","url":"https://assets-eu.researchsquare.com/files/rs-4212370/v1/eb76bb85e0b111cad136384b.png"},{"id":54572972,"identity":"1d8a7f55-d4fd-420f-84ae-5de9c421f36d","added_by":"auto","created_at":"2024-04-12 13:11:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":264904,"visible":true,"origin":"","legend":"\u003cp\u003ePurposed model of potential physiological associations of EDCs with the obesity in humans.\u003c/p\u003e","description":"","filename":"EDCsobesogens.JHPN.png","url":"https://assets-eu.researchsquare.com/files/rs-4212370/v1/fbf1ed16a28265ac340bac7c.png"},{"id":54572976,"identity":"1ca8775c-5d92-4594-885e-379de24c3c4e","added_by":"auto","created_at":"2024-04-12 13:11:59","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":403435,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flow diagram of the study selection process. Association of endocrine disrupting chemicals with obesity.\u003c/p\u003e","description":"","filename":"fig.3JHPN.png","url":"https://assets-eu.researchsquare.com/files/rs-4212370/v1/10bdba251199226dbda5987a.png"},{"id":64186094,"identity":"9a06196e-10a2-46be-9046-65447f22be8e","added_by":"auto","created_at":"2024-09-09 16:24:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1068084,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4212370/v1/08a6b1cb-74fc-4e7c-815a-bde975d35b45.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The endocrine disrupting chemicals and obesity prevention - Scoping review","fulltext":[{"header":"Introduction","content":"\u003cp skip=\"true\"\u003eThe excess body weight limit human performance, especially in ergonomically demanding occupations. For ergonomically demanding professions it is therefore important to ensure safety and preventive measures at work. Both, the excess weight, and the environmental excesses of different contaminants are accompanied by different health problems (Amato et al., 2021; Runkel et al., 2021; Srnovr\u0026scaron;nik et al., 2023; Tkalec et al., 2021; Woodruff et al., 2023). The environmental chemicals interrupting endocrine system known as endocrine disrupting chemicals (EDCs) are associated with reproductive complications, hormone-sensitive cancers, problems with thyroid function, changes of neuroendocrine systems and microbiota, diabetes, and obesity (Gore et al., 2015). Much research in recent years has focused on understanding plausible mechanisms underlying actions of endocrine disrupting chemicals (EDCs) and how human and animal exposures, especially during development, may lay the foundations for disease later in life. Environmental stressors such as EDCs are classified as potential obesogens, substances that cause obesity, but more profound conclusions based on experimental human studies are needed (Haverinen et al., 2021). General objective of the minimization of EDCs exposure and body burden is a pertinent central goal of the European regulation. The major current focus of EDCs research is epigenetics, microbiome, safe chemistry, dose-response functions of EDCs and their effects, and metabolism. Definitions of substances with endocrine-disrupting activities are now present in the EU regulation in the context of plant protection products and biocides. While threshold values of widely present pseudo-persistent chemicals are known, the specific test for other EDCs identifications and EU regulations are required (EP, 2019). The recent findings suggest that EDCs, especially bisphenol A (BPA), during all life stages correlates with increased body weight and/or body mass index, adipogenesis, adipose tissue inflammation, lipids, and glucose dysregulation, thus contributing to the weight gain and pathophysiology of obesity (Kumar et al., 2020; Darbre, 2017; Naomi et al., 2022; Legeay \u0026amp; Faure, 2017). Studies demonstrated the EDCs can bind to different hormone receptors (Figure 1), mostly those for estrogens, with specific agonistic or antagonistic effects and responses (De Coster \u0026amp; van Larebeke, 2012; Kim \u0026amp; Lee, 2017). The estrogens preserve the integrity of energy homeostasis at central and peripheral levels via nuclear and extranuclear pathways in both females and males (Mahboobifard et al., 2022). Moreover, some studies confirmed that BPA exerts its disrupting effects on the classical nuclear receptors such as estrogen receptors alpha and beta (ERa and ERb), non-classical membrane estrogen receptor (ncmER), estrogen-related receptor gamma (ERRg), G protein- coupled receptor 30 (GPR30), and the aryl hydrocarbon receptor (AhR) (Alonso-Magdalena et al., 2012). Through these interactions, BPA is thought to be involved in the onset of metabolic dysfunction. We need to take a closer look at EDCs to understand their impact on health and obesity in humans. The aim of this review was to summarize the current evidence regarding environmental EDCs \u0026ndash; bisphenols \u0026ndash; bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS), parabens, phthalates, and triclosan, and their association with obesity (Figure 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis review article focuses on the following endocrine disrupting chemicals:\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBisphenols\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBisphenol A (BPA;\u0026nbsp;4,4\u0026prime;-(Propane-2,2-diyl) diphenol; C\u003csub\u003e15\u003c/sub\u003eH\u003csub\u003e16\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e) is a synthetic chemical compound which was developed in the 1890s and its effect on estrogen activity was recognized in 1930s (Richter et al., 2007). BPA has been used in many consumer products including plastics (as a polymer); polycarbonate plastic (PVC), food packaging, dental sealants, and thermal receipts. Humans are exposed to BPA through their diet, inhalation of household dust, and dermal exposure (Wetherill et al., 2007, Carwile et al., 2009).\u0026nbsp;Moreover, due to\u003cem\u003e\u0026nbsp;\u003c/em\u003ehealth concerns BPA was largely replaced by bisphenol F \u003cem\u003e(BPF; 4,4\u0026prime;-Methylenediphenol; C\u003csub\u003e13\u003c/sub\u003eH\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e)\u003c/em\u003e and bisphenol S \u003cem\u003e(BPS; 4,4\u0026prime;-Sulfonyldiphenol; C\u003csub\u003e12\u003c/sub\u003eH\u003csub\u003e10\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS)\u003c/em\u003e, which resulted in increased production of BPF and BPS over the last few decades (F\u0026uuml;rhacker et al., 2000). However, it was found that both BPS and BPF are toxic and have the potential to interrupt metabolic action like BPA with some exceeding that of BPA (Vinas \u0026amp; Watson, 2013). \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParabens\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParabens (PBs), chemically a series of parahydroxybenzoates or esters of parahydroxybenzoic acid (also known as 4-hydroxybenzoic acid) include a group of chemicals which are used as preservatives in the food, cosmetic and pharmaceutical industries (Cashman \u0026amp; Warshaw, 2005). Their estrogenic effects were associated with the endocrine organs and other tissues, including adipose tissue. Several of these chemicals are known to cause obesogenic effects. In some experimental studies, it was found that there are some important associations between methylparaben exposure and adipsin, affecting energy balance in the body and metabolic health thus indicating its obesogenic potential (Kolatorova et al., 2018). In human biomonitoring PBs levels were associated with canned food and use of personal care products such as makeup and skin products (Sanchis et al., 2019; Tkalec et al., 2021).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTriclosan\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTriclosan (TCS;\u0026nbsp;5-Chloro-2-(2,4-dichlorophenoxy) phenol; C\u003csub\u003e12\u003c/sub\u003eH\u003csub\u003e7\u003c/sub\u003eCl\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e) developed in 1966 (\u003ccite\u003eBoyce \u0026amp; Pittet, 2002)\u003c/cite\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003eis usually found in personal care products as an antibacterial agent. In animal studies, TCS exposure was associated with androgenic and thyroid disturbance, contact dermatitis, and skin irritation (\u003ccite\u003eThompson\u003c/cite\u003e et al., 2005). Beside the estrogenic and androgenic effects in mammals, some studies suggest the potential of TCS to trigger antibiotic resistance (Goodman et al., 2018; Runkel et al., 2022).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePhthalates\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePhthalates, esters of phthalic acid (C\u003csub\u003e6\u003c/sub\u003eH\u003csub\u003e4\u003c/sub\u003e(CO\u003csub\u003e2\u003c/sub\u003eH)\u003csub\u003e2\u003c/sub\u003e), are chemicals which are used to improve the utility of plastics and personal care products in daily life (Kumari \u0026amp; Pulimi, 2023). A high-molecular-weight phthalates can enable flexibility of plastics, and are used as components in toys, building materials, medical devices, and paints. Meanwhile, low-molecular-weight phthalates are usually used as components of personal care products and cosmetics such as shampoos, lotions, nail care products, and other personal hygiene products. In general, phthalates are well-known EDCs with anti-androgenic effects (Lee et al., 2022). \u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eThis scoping review was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA, Figure 3) guideline (Tricco et al., 2018). We conducted an electronic literature search utilizing the National Library of Medicine (PubMed) database. The following medical subject heading (MESH) keywords were used to search for studies reporting on the role of environmental endocrine disruptors in the occurrence of obesity: \u0026lsquo;\u0026apos;endocrine disruptors\u0026rdquo; OR \u0026ldquo;endocrine disrupting chemicals\u0026rdquo; AND \u0026ldquo;obesity\u0026rdquo;.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSelected Literature\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe focus of the literature selection was to investigate the effects of pseudo-persistent EDCs such as BPA, parabens, phthalates and triclosan in studies. The database was searched for studies published in a decade from May 2013 until December 2023. Included studies were experimental studies (randomized control studies, case-control studies, cross-sectional studies, pilot studies or cohort studies), and meta-analyses. Studies published in languages other than English, were excluded from this review. We also performed a hand search of the reference lists of full-text articles that met our criteria in the primary literature search. All manuscripts and abstracts were independently reviewed by investigators for possible study inclusion regarding their subject and quality. The selected articles were read in full to confirm eligibility and to extract data. Studies and manuscripts were confirmed by all researchers included.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Extraction\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter primary search, we identified 245 potentially eligiable citations. Based on our inclusion criteria, we selected 12 studies for initial screening. By reviewing the references lists of selected studies, we revealed no additional potentialy eligiable citations. Studies that met our inclusion criteria identified possibble association of exposure to main EDCs (bisphenols, parabens, triclosans and phthalates) with obesity or overweight (Table 1). Figure 3 presents a PRISMA flow diagram of the association of EDCs with obesity.\u003c/p\u003e\n\u003cp\u003eFrom included studies, the following information was extracted for detailed evaluation: characteristics of the included studies (authors and year of publication), study design characteristics (sample type, sample size), methods (analyses, exposure), type of outcome assessment (type of endocrine disruptor) and the main findings (conclusions).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eStudies identifying possible association of obesity with the exposure to endocrine disrupting chemicals (EDCs). The data on experimental studies, meta-analyses and systematic review studies are presented in Table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLiterature Identification\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe possible effects of endocrine disrupting chemicals on obesity in humans described in experimental studies and meta-analysis are summarized in Table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe possible effects of endocrine disrupting chemicals on obesity in humans.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"605\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFirst author, year\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.47107438016529%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy design,\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSample size\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnalysis,\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eExposure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome assessment\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.677685950413224%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003eDirinck et al., 2016\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.47107438016529%\" valign=\"top\"\u003e\n \u003cp\u003eCohort study,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e184 metabolically\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eunhealthy obese (MUO)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;and metabolically healthy obese (MHO) males (53)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eand females (131)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e6 and 12 months of weight loss protocol (lifestyle counseling or bariatric surgery)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eSerum EDCs (PCB) levels, metabolic health data (body weight, blood pressure, lipids, inflammation, glucose metabolism)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.677685950413224%\" valign=\"top\"\u003e\n \u003cp\u003eHigher serum concentrations of PCBs in MUO compared to MHO. Concentration of PCBs does not differ after weight loss.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003eBrown et al.,\u003c/p\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.47107438016529%\" valign=\"top\"\u003e\n \u003cp\u003eObservational study,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27 obese adults with laparoscopic bariatric surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eAnalyses of EDCs during weight loss\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eBiological measurements of different EDCs (venous blood, urine)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.677685950413224%\" valign=\"top\"\u003e\n \u003cp\u003eEDCs (POPs) levels increased as weight loss occurred.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003eLiu et al.,\u003c/p\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.47107438016529%\" valign=\"top\"\u003e\n \u003cp\u003eProspective study,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRandomized clinical trial, 621 overweight and obese adults\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eEnergy restricted diets on weight changes (4 different macronutrient diet protocols)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eEDCs (PFASs), biological samples (glucose, lipids, thyroid hormones, leptin), RMR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.677685950413224%\" valign=\"top\"\u003e\n \u003cp\u003eHigher baseline PFASs levels were associated with greater decrease in RMR.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003eGuo et al.,\u003c/p\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.47107438016529%\" valign=\"top\"\u003e\n \u003cp\u003eClinical Trial,\u003c/p\u003e\n \u003cp\u003ePilot Study,\u003c/p\u003e\n \u003cp\u003e15 female adults: 8 obese/overweight and 7 with normal weight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e2 months of antioxidant intervention\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eBiological samples of EDCs (blood PCBs)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.677685950413224%\" valign=\"top\"\u003e\n \u003cp\u003eVitamin C\u0026nbsp;s (1000\u0026nbsp;mg/day) decreases body burden of POPs .\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003eMenale et al.,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2015\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.47107438016529%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eIn vitro\u003c/em\u003e exposure of human adipocytes to BPA,\u003c/p\u003e\n \u003cp\u003e8 non-obese prepubescent boys\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eEvaluated doses of BPA that interfere with estrogen function in metabolism\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eEDCs (BPA), biological samples (adipose cells from subcutaneous tissue)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.677685950413224%\" valign=\"top\"\u003e\n \u003cp\u003eBPA in mature adipocytes lead to molecular changes promoting metabolic disorders.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003ePredieri et al.,\u003c/p\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.47107438016529%\" valign=\"top\"\u003e\n \u003cp\u003eMeta-analysis\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eincluding experimental/epidemiological animal and human studies (n=65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003ePredispositions of T1D development and EDCs exposure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eExposure to EDCs in patients with T1D\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.677685950413224%\" valign=\"top\"\u003e\n \u003cp\u003eFurther studies with advanced biological techniques are needed to clarify risk factors of different mechanisms of T1D.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003eRibeiro et al.,\u003c/p\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.47107438016529%\" valign=\"top\"\u003e\n \u003cp\u003eSystematic Review,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMeta-analysis including\u003c/p\u003e\n \u003cp\u003e73 studies on (mostly cross-sectional design)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eAddressing an association of EDCs and anthropometric measures of obesity/body fat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eEDCs (BPA, phthalates, parabens) and obesity level or body fat\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.677685950413224%\" valign=\"top\"\u003e\n \u003cp\u003eBPA and phthalates associated with general and abdominal obesity.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003eLee et al.,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.47107438016529%\" valign=\"top\"\u003e\n \u003cp\u003eSystematic Review,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMeta-analysis including\u003c/p\u003e\n \u003cp\u003e22 longitudinal and 17 cross-sectional studies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eAnalyses of prenatal and postnatal EDCs exposure association with growth disturbances.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eEDCs (phthalate) exposure and body mass index (BMI) and fat mass\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.677685950413224%\" valign=\"top\"\u003e\n \u003cp\u003ePrenatal\u003c/p\u003e\n \u003cp\u003ephthalate exposure associated with low BMI, but not with body fat mass.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003eWassenaar \u0026amp; Legler,\u003c/p\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.47107438016529%\" valign=\"top\"\u003e\n \u003cp\u003eSystematic Review,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMeta-analysis including\u003c/p\u003e\n \u003cp\u003e31 animal studies on body and fat weight\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eAnalyses of obesogenic effects of phthalates in rodents\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eEDCs (phthalates), obesity data (body weight, fat weight, triglycerides, free fatty acids, leptin)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.677685950413224%\" valign=\"top\"\u003e\n \u003cp\u003eEarly life exposure to phthalates is potentially associated with increased adiposity in rodents.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003eHwang et al., 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.47107438016529%\" valign=\"top\"\u003e\n \u003cp\u003eMeta-analysis including\u003c/p\u003e\n \u003cp\u003e16 studies (12 cross-sectional, 2 case-control, 1 prospective study)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eRisk evaluation of T2DM and BPA\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eUrine and serum EDCs (BPA), T2DM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.677685950413224%\" valign=\"top\"\u003e\n \u003cp\u003eBPA exposure positively associated with T2DM risk in humans.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003eMendes et al., 2021\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.47107438016529%\" valign=\"top\"\u003e\n \u003cp\u003eSystematic Review,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMeta-analysis including\u003c/p\u003e\n \u003cp\u003e31 studies (mostly cross-sectional approach)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eAssociation analyses of EDCs, adiposity and diabetes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eEDCs (chlordane) levels, obesity, diabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.677685950413224%\" valign=\"top\"\u003e\n \u003cp\u003eData did not allow to reach clear conclusion regarding the association with adiposity.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003eGolestanzadeh et al., 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.47107438016529%\" valign=\"top\"\u003e\n \u003cp\u003eMeta-analysis including\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e99 studies (17 cohort, 15 cross-sectional, 3 case-control studies)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eAssociation analyses between EDCs and cardiometabolic risk factors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003eEDCs (phthalates), obesity level in children and adolescents\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.677685950413224%\" valign=\"top\"\u003e\n \u003cp\u003eA positive association between phthalate and some cardiometabolic risk factors.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eLegend:\u003c/strong\u003e PCBs-polychlorinated biphenyls; MUO-metabolically unhealthy obese; MHO-metabolically healthy obese; POPs-persistent organic pollutants; EDCs-endocrine disrupting chemicals; PFAS- Perfluoroalkyl substances; RMR-resting metabolic rate; T1D- type 1 diabetes; T2DM-Type 2 diabetes mellitus; BMI- body mass index.\u003c/p\u003e\n\u003cp\u003eThe main conclusions of 12 reviewed studies indicate that some obesity indications such as adipocytes changes, fat mass and RMR might be related with EDCs exposure (Dirinck et al., 2016; Brown et al., 2019; Liu et al., 2018; Menale et al., 2015; Ribeiro et al., 2020; Lee et al., 2022; Wassenaar \u0026amp; Legler, 2017; Hwang et al., 2018, Golestanzadeh et al., 2019) while some data did not allow to reach clear conclusions regarding EDCs with adiposity or cardiometabolic risk factors (Predieri et al., 2020; Mendes et al., 2021). In addition, researchers also suggested that antioxidant intervention might decrease the negative effects of studied EDCs (Guo et al., 2016).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe have reviewed experimental studies, meta-analyses, and systematic reviews regarding a general association between obesity and exposure to widely present environmental endocrine-disrupting chemicals (EDCs). Environmental stressors such as EDCs with broad implications, including the potential development of health symptoms, diseases and performance limitations in pilots should not be neglected. This review argues the importance of environmental exposure control as a tool to promote preventive health behaviors in pilots. Research findings of 12 studies were included and they suggest that EDCs may play a role in the current epidemiology of obesity.\u003c/p\u003e \u003cp\u003eObesity and overweight identification, treatment, and prevention present major public health challenges in multiple perspectives globally (WHO, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). The physiopathology and clinical impacts of excess body fat (BF) are incompletely understood, and there are many difficulties in developing safe and effective long-term therapeutic strategies (Heymsfield \u0026amp; Wadden, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). Specifically, a higher blood levels of EDCs in metabolically unhealthy obese persons compared to metabolically healthy obese persons were demonstrated in experimental studies. Interestingly, the weight loss protocols did not change the EDCs levels in biological samples (Dirinck et al., \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2016\u003c/span\u003e), or the level of EDCs even increased as weight loss occurred (Brown et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Moreover, higher level of EDCs was associated with greater weight regain explained with greater decrease in resting metabolic rate (Liu et al., \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Researchers evaluating environmentally relevant doses of EDCs that interfere with estrogen function in metabolism found some molecular changes which promote metabolic disorders (Menale et al., \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). In addition, potential vitamin supplementations were analyzed to reduce toxic effects of EDCs, which needs to be further investigated (Guo et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Conclusions of meta-analyses show EDCs as obesogenic (Riberiro et al., 2020, Wasseraar \u0026amp; Legler, 2018) and suggest the association of EDCs with type 2 diabetes mellitus (Hwang et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2018\u003c/span\u003e) and cardio-vascular risk (Dirinck et al., \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2016\u003c/span\u003e, Golestanzadeh et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). In addition, the EDCs were associated with generalize and abdominal obesity (Ribeiro, 2020).\u003c/p\u003e \u003cp\u003eTrans-generational inheritance and bioaccumulation of EDCs are clear obstacles for new research evidence (Laureta et al., 2019). Prenatal life exposure to EDCs was associated with low body mass index (BMI) (Lee et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) and increased level of fat mass in children (Wassenaar \u0026amp; Legler, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). More studies are warranted to elucidate the mechanisms underlying the link between EDCs exposure and metabolic health (Liu et al., \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). EDCs are lipophilic environmental toxicants and as such bio-accumulate in adipose tissues thus presenting increasing health hazards in individuals with excess body weight (Brown et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Weight loss was related to the release and redistribution of organic pollutants to other lipid-rich organs such as the brain, kidney, and liver, which needs further investigations. It was suggested that even weight control interventions should be considered to limit organ exposure to pollutants when weight loss protocols are planned. Moreover, in diet induced weight-loss, higher baseline plasma EDCs concentrations were significantly associated with greater weight regain, especially in women, accompanied by a slower regression of resting metabolic rate (Liu et al., \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). It is necessary to understand the complexity of the mechanisms which are involved in differentiation of fat cells and the influence of EDCs in the adipogenesis and the etiology of obesity (Gonz\u0026aacute;lez-Casanova et al., \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). The findings indicate a significant association between exposure to BPA and obesity in adults but are insufficient to support that EDCs cause obesity \u0026ldquo;per se\u0026rdquo; in humans due to the cross-sectional design of most included studies (Ribeiro et al., \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Gonz\u0026aacute;lez-Casanova et al. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) reported that EDCs can alter lipid metabolism, promote fat accumulation, and interfere with processes such as adipogenesis through the immunomodulation effects and other mechanisms of action such as microbiota and epigenetics. Findings on animal\u0026rsquo;s immune and inflammatory responses support the idea that further investigations are needed in human, to better understand the health consequences of EDCs exposure.\u003c/p\u003e \u003cp\u003eHowever, humans may be exposed to more EDCs at the same time and exposure varies over time, what makes it impossible to evaluate theirs potential synergistic or antagonistic effects. As well, it is important that EDCs have a very short urinary elimination half-life in the human body and it may be necessary to consider if a single urine or blood sample is representative of the overall exposure of an individual, including the subjective level of daily environmental exposure. EDCs act via various hormone receptors through a variety of known and unknown mechanisms including epigenetic modifications. They differ from classic toxins in several ways such a slow-dose effect (time after exposure), non-monotonic dose and trans-generational effects.\u003c/p\u003e \u003cp\u003eSpecifically, the results of included studies suggested that BPA is associated with obesity and may negatively affect the metabolic functions in various ways. Some epidemiological studies which were using data from the National Health and Nutrition Examination Survey (NHANES) reported that higher urine BPA concentrations tend to be correlated with greater obesity risk and waist circumference (Shankar et al., \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Bhandari et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Researchers confirmed a significant relationship between BPA and childhood obesity (Kim \u0026amp; Lee, 2019). Menale at al. (2015) described the role of BPA in modulating canonical endocrine function, which regulates metabolism during childhood. It was reported that BPA at environmental doses acts in mature adipocytes by modulating gene expression, which leads to molecular changes that promote metabolic disorders in children. The persistence of BPA in the environment and in the human adipose tissue might be an important risk factor and a strong argument for further research of the obesity development (Menale et al., \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2015\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWassenaar \u0026amp; Legler (\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2017\u003c/span\u003e) reported that early life exposure of animals to phthalates is associated with increased fat weight, while non-significant negative association was associated with body weight. On the other hand, studies on the association between exposure to phthalates in childhood and obesity were inconsistent. Specifically, prenatal phthalate exposure may disturb the normal growth of children by decreased BMI rather than causing obesity, as hypothesized by previous studies (Lee et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Moreover, it was recently discovered that BPA and phthalates are cardiovascular disruptors and BPA by itself could have a direct relationship with systemic inflammation regardless of obesity or insulin resistance.\u003c/p\u003e \u003cp\u003eParabens were related with obesogenic potential affecting energy balance and metabolic health (Kolatorova et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). While contradictory results were obtained regarding triclosan and obesity, one of recent animal studies emphasized the underlying toxic obesogenic mechanism of triclosan which is based on gut-brain axis (Wang et al., \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). However, the relationship between triclosan and parabens with obesity remains unclear and inconclusive, and further research is needed.\u003c/p\u003e \u003cp\u003eIncreased exposure to EDCs could pose long-term health risk effects. EDCs are ubiquitous contaminants with a broad spectrum of effects. The chemicals such as BPA, parabens, triclosan and phthalates are common environmental pollutants which are incriminated for metabolic as well as a reproductive disorders. Therefore, most published literature concerning EDCs and obesity is limited mostly to diabetes and BPA. Therefore, human research combining biomonitoring, analyses of biological samples, and structured questionnaire of life-quality, food and physical activity to evaluate the association between lifestyle variables potentially related to EDCs could present one of the possible designs of more profound strategy to understand the association of EDCs and obesity.\u003c/p\u003e \u003cp\u003eHowever, the qualitative similarity of most data indicate that EDCs are related with obesity through various physiological pathways that may also lead to weight gain. Therefore, the conclusions thus might serve as an awareness to avoid the exposure of EDCs. This is particularly important in the current worldwide scenario of ongoing exposure of children and adults to EDCs, not only to chemicals which are still used for a wide range of purposes but also to compounds that were banned in many countries but have persistent and ubiquitous occurrence in the environment. To better illuminate the environmental triggers of obesity, further studies on larger populations are needed.\u003c/p\u003e \u003cp\u003eIn this review, we summarized the knowledge on the association of EDCs such as BPA, parabens, triclosan and phthalates with obesity in the last 10 years. Revealed studies, methodologically heterogenic, have reported a potential association between prolonged exposure to EDCs and obesity mainly through diabetes and metabolic disorders, while exact mechanisms remain scarce. However, main findings of this review need to be interpreted with caution due to used methodology investigating EDCs and obesity, selected database, and a small number of existing experimental studies. Recent research indicates that there is a specific need to combine human biomonitoring with other investigating methods to evaluate quality of life including exposure to environmental triggers such as plastic, and personal hygiene products of the observed population. More studies on molecular effects are needed to understand an association of EDCs with metabolic diseases, particularly human obesity. The exposure of environmental triggers and possible associations with human performance and disease prevention should not be neglected.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eOur scoping review has some limitations. Our literature search was limited to a single database and to publications available entirely in the English language, potentially excluding valuable research conducted in other languages and from other databases. Lastly, our results are only up to date as of December 2023, and any subsequent studies beyond this timeframe are not incorporated into our review.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eRegardless of some inconsistences in the findings across summarized studies, involuntary exposure to EDCs might be related with obesity development. Further studies including multicentric studies are needed to delineate exact mechanisms through which EDC exposure causes obesity so that efficient preventative measures could be implemented. The lack of public knowledge about the effects of EDCs on human health is worrying, which should induce health care providers to inform especially specific health population or ergonomically demanding populations to avoid the excess body weight and possible EDC exposure thus empowering them to make healthy choices.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have contributed to the article, read manuscript, agreed with the content, and approved the submitted version. Authors confirm that the manuscript is original and has not been published in a journal and is not currently under consideration by another journal. MA collected the data for paper, coordinated and contributed at all stages of the review and critically reviewed the final review. TK contributed to the writing of the review and contributed to the strategy development and in all stages of the review. IVK contributed to the writing of the paper and participated in all stages of data collection.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data gathered during this study are included in the published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAlonso-Magdalena P, Ropero AB, Soriano S, Garc\u0026iacute;a-Ar\u0026eacute;valo M, Ripoll C, et. al. 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World Health Organization; [accessed 2023, Oct 2]. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight/. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-health-population-and-nutrition","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"johp","sideBox":"Learn more about [Journal of Health, Population and Nutrition](http://jhpn.biomedcentral.com/)","snPcode":"41043","submissionUrl":"https://submission.nature.com/new-submission/41043/3","title":"Journal of Health, Population and Nutrition","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"bisphenols, parabens, triclosan, phthalates, obesity","lastPublishedDoi":"10.21203/rs.3.rs-4212370/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4212370/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eExposure to endocrine disrupting chemicals (EDCs) can result in alterations of natural hormones in the body. The aim of this review article is to gather current knowledge about EDCs and obesity in humans. We conducted an electronic literature search using PubMed platform for studies published between y. 2013-2023 on EDCs and obesity. A total of 12 studies met our inclusion criteria focusing on more prominent EDCs such as bisphenols, parabens, triclosan, and phthalates, and their association with obesity. A few experimental studies have been performed on association of obesity and EDCs in humans. Obesity was mostly related to EDCs such as bisphenols and phthalates, while less is known about the impact of parabens and triclosan. Series of negative physiological effects involving obesogenic, diabetogenic, and inflammatory mechanisms, epigenetic and microbiota modulations were related to prolonged EDCs exposure. More profound research of obesity with specific design regarding its role, genetic background for diabetes-related features, cardiometabolic risks and anthropometrical exceeds are needed to illuminate the effect of EDCs exposure on human populations in different environments.\u003c/p\u003e","manuscriptTitle":"The endocrine disrupting chemicals and obesity prevention - Scoping review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-12 13:11:34","doi":"10.21203/rs.3.rs-4212370/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-04-26T09:53:11+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-04-17T09:18:56+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-04-11T13:47:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"e7c7616b-66eb-4338-90ce-6112962a2e92","date":"2024-04-11T07:12:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"18e8da4f-5600-4c25-9254-bec475e77927","date":"2024-04-11T01:11:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"15b88d75-3200-46ac-84ec-3cdb41954401","date":"2024-04-10T18:39:02+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-10T18:13:22+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-09T07:00:55+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-04T12:23:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Health, Population and Nutrition","date":"2024-04-03T11:26:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-health-population-and-nutrition","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"johp","sideBox":"Learn more about [Journal of Health, Population and Nutrition](http://jhpn.biomedcentral.com/)","snPcode":"41043","submissionUrl":"https://submission.nature.com/new-submission/41043/3","title":"Journal of Health, Population and Nutrition","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"94ea2de5-4342-417c-9199-79f3cd39e3ab","owner":[],"postedDate":"April 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-09-09T16:15:25+00:00","versionOfRecord":{"articleIdentity":"rs-4212370","link":"https://doi.org/10.1186/s41043-024-00627-y","journal":{"identity":"journal-of-health-population-and-nutrition","isVorOnly":false,"title":"Journal of Health, Population and Nutrition"},"publishedOn":"2024-09-03 16:05:49","publishedOnDateReadable":"September 3rd, 2024"},"versionCreatedAt":"2024-04-12 13:11:34","video":"","vorDoi":"10.1186/s41043-024-00627-y","vorDoiUrl":"https://doi.org/10.1186/s41043-024-00627-y","workflowStages":[]},"version":"v1","identity":"rs-4212370","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4212370","identity":"rs-4212370","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}