The increasing usage of bisphenol S (BPS) analogs as novel alternatives to bisphenol A (BPA) or BPS results in widespread exposure risks. In contrast to BPS, BPS analog-induced perturbations in lipid metabolism are largely unknown. Our study aimed to investigate the interactions of nine novel BPS analogs with peroxisome proliferator-activated receptor γ (PPARγ) and their impacts on 3T3-L1 adipogenesis. BPS and its analogs were found to have varying binding affinities to the PPARγ ligand-binding domain, and five of the BPS analogs were identified as novel PPARγ agonists as evidenced by increased expressions of the PPARγ mediated luciferase reporter gene. Interestingly, seven BPS analogs, including five BPS analogs with PPARγ agonistic potency and two BPS analogs with negligible binding affinity, exhibited comparable or even greater adipogenic effects than BPS, which were demonstrated by increased triglyceride accumulation and enhanced expressions of the adipogenic biomarkers in 3T3-L1 cells. Further comparison revealed that a phenoxy group may be a potential structural regulator for the adipogenic capacities of the test BPS analogs. The findings provided the first evidence that seven novel BPS analogs exerted adipogenic potentials through PPARγ or other signaling pathways, revealing a hidden environmental factor in the development of obesity and other lipid metabolism disorders.

There is growing concern about the concept that exposure to environmental chemicals may be contributing to the obesity epidemic. However, there is no consensus on the obesogenic effects of emerging contaminants from a toxicological and environmental perspective. The potential human exposure and experimental evidence for obesogenic effects of emerging contaminants need to be systematically discussed. The main objective of this review is to provide recommendations for further subsequent policy development following a critical analysis of the literature for humans and experimental animals exposed to emerging contaminants. This article reviews human exposure to emerging contaminants (with a focus on antimicrobials, preservatives, water and oil repellents, flame retardants, antibiotics and bisphenols) and the impact of emerging contaminants on obesity. These emerging contaminants have been widely detected in human biological samples. Epidemiological studies provide evidence linking exposure to emerging contaminants to the risks of obesity in humans. Studies based on animal models and adipose cells show the obesogenic effects of emerging contaminants and identify modes of action by which contaminants may induce changes in body fat accumulation and lipid metabolic homeostasis. Some knowledge gaps in this area and future directions for further investigation are discussed.

Exposure to metabolism-disrupting chemicals (MDCs), compounds largely belonging to the group of endocrine-disrupting chemicals (EDCs), is associated with metabolic dysfunctions such as dyslipidemia, insulin resistance and hepatic steatosis. Steroid hormone receptors (SHRs) are known targets for MDCs but their regulatory environment in the presence of environmental chemicals remains elusive. Here, we studied the activation and molecular interactions of SHRs exposed to 17 suspected MDCs including pesticides, plasticizers, pharmaceuticals, flame retardants, industrial chemicals and their metabolites by combining in vitro and in silico approaches. We first established and pre-validated reporter gene assays in HepG2 hepatoma cells to assess the activation of estrogen (ER), androgen (AR), glucocorticoid (GR) and progesterone (PR) receptors. Next, using RNA-seq and publicly available protein interaction data, we identified relevant SHR-interacting coregulators expressed in hepatic cells and measured their MDC-dependent interactions with SHRs using the Microarray Assay for Real-time Coregulator-Nuclear receptor Interaction (MARCoNI) technology. Finally, we examined MDC binding to ER and GR using molecular dynamics simulations. These combined approaches lead to identification of MDCs capable of SHR activation at picomolar-to-low micromolar concentrations and paralleled with their ability to induce recruitment of multiple coregulators. MDCs induced distinct SHR-coregulator binding patterns involving multiple coactivators, corepressors and other modulatory proteins. Our results have broadened the test battery to detect MDCs and indicate that the activation of SHRs by MDCs is driven by diverse molecular interactions.

Bisphenol S (BPS) is a widely detected environmental toxin with the potential to increase the risk of non-alcoholic fatty liver disease (NAFLD). However, the effects of BPS on the progression of high fat diet (HFD)-induced NAFLD remain unclear. This study aimed to explore the role and underlying mechanisms of action of BPS in HFD-induced NAFLD. Our results showed that BPS exposure (50 and 500 μg/kg bodyweight/day) promoted the progression of NAFLD, which was evidenced by increased liver/body weight ratio, elevated serum alanine aminotransferase and aspartate aminotransferase levels, and more and larger lipid droplets in liver tissues. These phenomena were accompanied by abnormal expression levels of fatty acid uptake (Cd36), fatty acid synthesis (Pparγ, Scd-1, and Fasn), fatty acid oxidation (Pparα), and cytokines (TNFα, IL-1β, and IL-6). In vitro and in vivo studies showed that BPS exposure caused hepatic ferroptosis by regulating ferroptosis-related markers (GPX4, xCT, FTH, and ACSL4). Moreover, BPS exposure caused ROS overproduction, mitochondrial dysfunction, lipid peroxidation, and GSH suppression, all of which were restored by ferrostatin-1, a ferroptosis inhibitor. Moreover, BPS significantly upregulated HMGCS2 expression in the hepatocytes and liver tissues. 3-hydroxy-3-methylglutaryl coenzyme A synthetase 2 (HMGCS2) knockdown mitigated the effects of BPS on hepatocytes and reversed the expression of ferroptosis-related markers. Thus, BPS exposure aggravates HFD-induced NAFLD by regulating HMGCS2-mediated ferroptosis. Collectively, our study indicates that BPS exposure at environmentally relevant concentrations may aggravate NAFLD phenotypes under HFD conditions, highlighting the health risks of BPS to the liver.

BPF is a ubiquitous environmental chemical that has been shown to affect neurodevelopmental toxicity from animals to humans. Whether BPF exposure affects neural stem cell proliferation and differentiation is unknown. Here, we utilized a method of permeabilization of Drosophila embryos to analyze the effects of exposure to 0.5 mM, 1 mM, and 2 mM BPF on the proliferation and differentiation of neural stem cells. Our results showed that BPF exposure reduced the number of neuroblasts and intermediate neural progenitors during the embryonic stage, which caused the neuron/glial cell ratio to be out of balance, with a decrease in the number of neurons and an increase in the number of glial cells. BPF exposure caused neurotoxicity by reducing the activities of the antioxidant enzymes CAT and SOD, the downregulation of the transcriptional levels of oxidative stress-related genes, which triggered oxidative damage. As a result, embryonic BPF exposure affected the development of the neuromuscular junctions (NMJs) by reducing the number of axon branches and synaptic buttons, decreasing the number of peristaltic contractions, and reducing larval locomotion. In conclusion, our results demonstrate that embryonic BPF exposure disrupts neural stem cell proliferation, causing neurodevelopmental toxicity and abnormal larval behavior.

Human health depends on planetary health, and yet healthcare provision can have unintended consequences for the health of the planet. Emissions from the healthcare sector include greenhouse gases, air pollution and plastic pollution, alongside chemical contamination. Chemical pollution resulting in endocrine disruption has been associated with plastics, which are a source of concerning additives such as phthalates, bisphenols, perfluoroalkyl and polyfluoroalkyl substances, and flame retardants (all routinely found in healthcare products). Many endocrine-disrupting chemicals are persistent and ubiquitous in the environment (including water and food sources), with potential secondary harms for human health, including disrupting reproductive, metabolic and thyroid function. Here we review evidence-based strategies for mitigating environmental effects of healthcare delivery. We focus on what endocrinologists can do, including reducing demand for healthcare services through better preventative health, focusing on high-value care and improving sustainability of medical equipment and pharmaceuticals through adopting circular economy principles (including reduce, reuse and, as a last resort, recycle). The specific issue of endocrine-disrupting chemicals might be mitigated through responsible disposal and processing, alongside advocating for the use of alternative materials and replacing additive chemicals with those that have lower toxicity profiles, as well as tighter regulations. We must work to urgently transition to sustainable models of care provision, minimizing negative effects on human and planetary health.

Early-life exposure to short half-life chemicals may influence adiposity growth, a precursor to obesity. Previous studies often relied on limited urine samples that inadequately represent exposure during pregnancy or infancy. Additionally, childhood adiposity is commonly estimated using body mass index, which does not accurately reflect body composition. We aimed to investigate associations between early-life exposures to phenols, parabens, phthalates and fat mass percent at 3 years of age among 341 mother-child couple from the SEPAGES cohort. We further assessed potential effect modification by sex.

We measured 8 phenols, 4 parabens, 13 phthalates and 2 non-phthalate plasticizer metabolites from weekly pooled urine sample collected from mothers during pregnancy (three urine samples a day, median 18 and 34 gestational weeks), and from their infant (one urine sample a day, at 2 and 12 months). Clinical examinations at 3 years included standardized skinfold thickness measurements and bioelectrical impedance analysis to calculate fat mass percentage.

Positive associations were identified between prenatal exposures to bisphenol S, mono-benzyl phthalate (MBzP), monoethyl phthalate (MEP), and mono-n-butyl phthalate and fat mass percentage at 3 years, while triclosan showed a negative association. MBzP and MEP showed effect modification by sex, with stronger associations among females. No significant associations were detected for postnatal exposures.

This study suggests associations between prenatal exposures to short half-life chemicals and percent fat mass in preschool children. Furthermore, this study is the first investigating the impact of prenatal bisphenol S exposure, highlighting the need for investigation of this overlooked compound.

Endocrine disruptors (EDs) can mimic or interfere with hormones in the body, leading to non-communicable diseases, such as obesity, diabetes, and metabolic syndrome. Susceptibility to EDs increases during prenatal and postnatal life, a critical time window. This review aims to summarize the latest evidence on the relation of early life exposure to some EDs with obesity and the other metabolic disorders.  RECENT FINDINGS: There is increasing evidence that early life exposure to EDs may impair adipogenesis by increasing the number and size of adipocytes, thereby increasing susceptibility to obesity in childhood. It is stated that exposure to EDs during the prenatal and postnatal period may raise the risk of type 2 diabetes in adulthood by disrupting glucose, lipid, and insulin homeostasis in the offspring. They can also accelerate the development of type 1 diabetes through various mechanisms, like immunomodulation, gut microbiota, and vitamin D pathways. There is a growing understanding that ED exposure during critical stages of life could play an important role in the development of obesity and metabolic disorders. We suggest setting national goals, global standards, and policies to reduce environmental exposure to pregnant and lactating women, and babies, considered sensitive populations.

The effects of plastics on human health include allergy, atopy, asthma, and immune disruption, but the consequences of chemicals used in plastic materials span nearly every organ system and age group as well. Behavioral interventions to reduce plastic chemical exposures have reduced exposure in low- and high-income populations, yet health care providers know little about plastic chemical effects and seldom offer steps to patients to limit exposure. Health care facilities also use many products that increase the risk of chemical exposures, particularly for at-risk populations such as children in neonatal intensive care units. Given that disparities in plastic chemical exposure are well documented, collaborative efforts are needed between scientists and health care organizations, to develop products that improve provider knowledge about chemicals used in plastic materials and support the use of safer alternatives in medical devices and other equipment.

Obesity, diabetes, and their cardiovascular and hepatic comorbidities are alarming public health issues of the twenty-first century, which share mitochondrial dysfunction, oxidative stress, and chronic inflammation as common pathophysiological mechanisms. An increasing body of evidence links the combined exposure to multiple environmental toxicants with the occurrence and severity of metabolic diseases. Endocrine disruptors (EDs) are ubiquitous chemicals or mixtures with persistent deleterious effects on the living organisms beyond the endocrine system impairment; in particular, those known as metabolism-disrupting chemicals (MDCs), increase the risk of the metabolic pathologies in adult organism or its progeny. Being largely lipophilic, MDCs mainly target the adipose tissue and elicit mitochondrial dysfunction by interfering with mitochondrial bioenergetics, biogenesis, dynamics and/or other functions. Plastics, when broken down into micro- and nano-plastics (MNPs), have been detected in several human tissues, including the liver. The harmful interplay between inflammatory and redox processes, which mutually interact in a positive feed-back loop, hence the term oxidative inflammation ("OxInflammation"), occurs both at systemic and organ level. In both liver and adipose tissue, oxinflammation contributes to the progression of the metabolic dysfunction-associated steatotic liver disease (MASLD). Moreover, it has been reported that individuals with MASLD may be more susceptible to the harmful effects of toxicants (mainly, those related to mitochondria) and that chronic exposure to EDs/MDCs or MNPs may play a role in the development of the disease. While liver has been systematically investigated as major target organ for ambient chemicals, surprisingly, less information is available in the literature with respect to the adipose tissue. In this narrative review, we delve into the current literature on the most studied environmental toxicants (bisphenols, polychlorinated biphenyls, phthalates, tolylfluanid and tributyltin, per-fluoroalkyl and polyfluoroalkyl substances, heavy metals and MNPs), summarize their deleterious effects on adipose tissue, and address the role of dysregulated mitochondria and oxinflammation, particularly in the setting of MASLD.

Bisphenol A (BPA), an obesogen, can disrupt adipogenesis in vitro, but these studies did not distinguish adipocytes as white or brown. BPA can be metabolized into BPA-glucuronide (BPA-G) and BPA-sulfate (BPA-S). These metabolites are not completely inactive in the body, but the related studies remain limited. In this study, preadipocytes isolated from mouse white and brown adipose tissues were treated with 0.1, 1, and 10 μM of BPA and its metabolites for 6 days, which are equivalent to the exposure level of general and occupational populations, to investigate and compare the effects of BPA and its metabolites on white and brown adipogenesis. The results showed that BPA and BPA-G increased lipid accumulation during white adipogenesis, whereas only BPA induced this same effect during brown adipogenesis. Moreover, BPA and its metabolites upregulated the expression of pan-adipogenic markers, such as peroxisome proliferator-activated receptor gamma (PPARγ), during white adipogenesis, whereas they downregulated that of PPARγ during brown adipogenesis. Additionally, BPA also inhibited the mRNA and protein expression of brown fat-specific markers (e.g., PPARγ coactivator 1-1alpha (PGC1-α) and uncoupling protein 1 (UCP1)), and mitochondrial activity during brown adipogenesis, and BPA-G also reduced the mRNA expression levels of Pgc1-α and Ucp1. These findings indicated that BPA induced different effects on white and brown adipogenesis, enhancing the former and hindering the latter. Despite less potent than BPA, BPA-G and BPA-S might also affect white and brown adipogenesis. This research provides in-depth insights into the obesogenic effects of BPA and the biological activities of its metabolites.

Bisphenol A (BPA) is a vital raw material used to manufacture various household and commercial goods. However, BPA is a contaminant of emerging concern (CEC) and an endocrine-disrupting chemical (EDC) capable of migrating and bio-accumulating in environmental and biological compartments. At threshold levels, they become toxic causing adverse health and environmental issues. BPA's occurrence in food, food contact materials (FCMs), beverages, water, cosmetics, consumer goods, soil, sediments, and human/biological fluids across Africa was outlined. Unlike most reviews, it further collated data on BPA remediation techniques, including the human and ecological risk assessment studies conducted across Africa. A systematic scrutiny of the major indexing databases was employed extracting relevant data for this study. Results reveal that only 10 out of 54 countries have researched BPA in Africa. BPA levels in water were the most investigated, whereas levels in cosmetics and consumer goods were the least studied. Maximum BPA concentrations found in Africa were 3,590,000 ng/g (cosmetic and consumer goods), 154,820,000 ng/g (soils), 189 ng/mL (water), 1139 ng/g (food), and 208.55 ng/mL (biological fluids). The optimum percentage removal/degradation of BPA was within 70-100%. The potential health and ecological risk levels were assessed by comparing them with recommended limits and were found to fall within safe/low risks to unsafe/high risks. In conclusion, this study revealed that there is still little research on BPA in Africa. Levels detected in some matrices call for increased research, stricter health and environmental regulations, and surveillance.

Every year the global incidence of obesity increases considerably and among the factors that favor it is bisphenol A (BPA), an endocrine disruptor widely used in plastics and omnipresent in many everyday objects.

A total of 19 studies published between 2018 and 2023 that addressed the relationship between BPA exposure and obesity were included in this review in order to better understand its behavior and mechanisms of action.

The studies reviewed conclude that BPA is an obesogen that alters the function of hormonal receptors, promotes metabolic syndrome, affects certain genes, etc., leading to a greater risk of developing obesity. With important emphasis on the ability to cause epigenetic changes, thus transmitting the effects to offspring when exposure has occurred during critical stages of development such as during gestation or the perinatal period.

There is sufficient evidence to show that BPA is a risk factor in the development of obesity. Even so, further research is necessary to exhaustively understand the causal relationship between the two in order to develop prevention measures and avoid possible future adverse effects.

Bisphenols, such as bisphenol A and its analogs, which include bisphenol S, bisphenol F, bisphenol AF, and tetramethyl bisphenol F, are chemical contaminants commonly found in food that raise serious health concerns. These xenobiotics can potentially have harmful effects on human health. The gut microbiota plays a crucial role in metabolizing and neutralizing these substances, which is essential for their detoxification and elimination. Probiotic supplementation has been studied for its ability to modulate the gut microbiota's composition and function, enhancing detoxification processes. Next-Generation Probiotics (NGPs) may exhibit better properties than traditional strains and are designed for targeted action on specific conditions, such as obesity. By modulating inflammatory responses and reducing the secretion of pro-inflammatory cytokines, they can significantly improve host health. Research on NGPs' ability to neutralize obesogenic bisphenols remains limited, but their potential makes this a promising area for future exploration. This review aims to understand the mechanisms of the chemical transformation of bisphenol through its interactions with the gut microbiota and the role of probiotics, particularly NGPs, in these processes. Understanding the interplay between bisphenols, gut microbiota, and NGPs may pave the way for strategies to counteract the negative health effects associated with daily and chronic exposure to bisphenols, which is crucial for food safety and consumer health protection.

Over the past three decades, there has been a significant increase in the prevalence and incidence of overweight and obesity worldwide. The obesogen hypothesis suggests that certain external agents may affect pathways related to fat accumulation and energy balance by stimulating fat cell differentiation and proliferation. Previous research has indicated that exposure to bisphenol A (BPA) and some of its analogues may influence fat accumulation by promoting the transformation of preadipocytes into adipocytes. This study aimed to assess the possible contribution of dietary bisphenol exposure to the odds of developing overweight and obesity in a sample of Spanish children according to sex.

Dietary and anthropometric data were collected from 179 controls and 124 cases schoolchildren aged 3-12 years. Dietary exposure to BPA and bisphenol S (BPS) was assessed using a food consumption frequency questionnaire. Logistic regression models were used to assess the influence of dietary exposure to bisphenols on overweight and obesity stratified by sex.

For females, cases had significantly higher exposure to BPA from meat and eggs compared to controls (median = 319.55, interquartile range (IQR) = 176.39-381.01 vs 231.79 (IQR) = 162.11-350.19, p-value = 0.046). Diet quality was higher for controls (6.21 (2.14) vs 4.80 (2.24) p < 0.001) among males independently of a high or low exposure to bisphenols. However, higher diet quality was observed for female controls with an high exposure of total bisphenols (6.79 (2.04) vs 5.33 (2.02) p = 0.031). Females exposed to high levels of BPA from meat and eggs had higher likelihood of being overweight and obese (adjusted Odds Ratio = 2.70, 95% confidence interval = 1.00 - 7.32). However, no consistent associations were found in males.

High BPA levels from meat and eggs were positively associated with overweight and obesity in females. The dietary intake of BPA in the schoolchildren in the present study was much higher than the acceptable daily intake established by EFSA for the last year.

Bisphenols and phthalates are two classes of endocrine-disrupting chemicals (EDCs) thought to influence weight and adiposity. Limited research has investigated their influence on maternal weight changes, and no prior work has examined maternal fat mass. We examined the associations between exposure to these chemicals during pregnancy and multiple maternal weight and fat mass outcomes.

This study included a sample of 318 women enrolled in a Canadian prospective pregnancy cohort. Second trimester urinary concentrations of 2 bisphenols and 12 phthalate metabolites were quantified. Self-reported and measured maternal weights and measured skinfold thicknesses were used to calculate gestational weight gain, 3-months and 3- to 5-years postpartum weight retention, late pregnancy fat mass gain, total postpartum fat mass loss, and late postpartum fat mass retention. Adjusted robust regressions examined associations between chemicals and outcomes in the entire study population and sub-groups stratified by pre-pregnancy body mass index (BMI). Bayesian kernel machine regression examined chemical mixture effects.

Among women with underweight or normal pre-pregnancy BMIs, MBzP was negatively associated with weight retention at 3- to 5-years postpartum (B = -0.04, 95%CI: -0.07, -0.01). Among women with overweight or obese pre-pregnancy BMIs, MEHP and MMP were positively associated with weight retention at 3-months and 3- to 5-years postpartum, respectively (B's = 0.12 to 0.63, 95%CIs: 0.02, 1.07). DEHP metabolites and MCNP were positively associated with late pregnancy fat mass gain and late postpartum fat mass retention (B's = 0.04 to 0.18, 95%CIs: 0.001, 0.32). Further, the mixture of EDCs was positively associated with late pregnancy fat mass gain.

In this cohort, pre-pregnancy BMI was a key determinant of the associations between second trimester exposure to bisphenols and phthalates and maternal weight changes and fat accumulation. Investigations of underlying physiological mechanisms, windows of susceptibility, and impacts on maternal and infant health are needed.

Bisphenols are a group of endocrine-disrupting chemicals used worldwide for the production of plastics and resins. Bisphenol A (BPA), the main bisphenol, exhibits many unwanted effects. BPA has, currently, been replaced with bisphenol F (BPF) and bisphenol S (BPS) in many applications in the hope that these molecules have a lesser effect on metabolism than BPA. Since bisphenols tend to partition into the lipid phase, their place of choice would be the cellular membrane. In this paper, I carried out molecular dynamics simulations to compare the localization and interactions of BPA, BPF, and BPS in a complex membrane. This study suggests that bisphenols tend to be placed at the membrane interface, they have no preferred orientation inside the membrane, they can be in the monomer or aggregated state, and they affect the biophysical properties of the membrane lipids. The properties of bisphenols can be attributed, at least in part, to their membranotropic effects and to the modulation of the biophysical membrane properties. The data support that both BPF and BPS, behaving in the same way in the membrane as BPA and with the same capacity to accumulate in the biological membrane, are not safe alternatives to BPA.

The current study aimed to explore whether bisphenol A (BPA) exposure aggravated the decrease in Tregs induced by ovalbumin (OVA) in adolescent female mouse models of asthma, and whether the process was associated with mTOR-mediated signaling pathways and DNA methylation levels. A total of 40 female C57BL/6 mice at the age of four weeks were used and divided into five groups after 1 week of domestication. Each group consisted of eight mice: the control group, OVA group, OVA + BPA (0.1 μg mL-1) group, OVA + BPA (0.2 μg mL-1) group, and OVA + BPA (0.4 μg mL-1) group. Results revealed that Foxp3 protein levels decreased in the spleens of mice exposed to BPA compared to those in the OVA group. After an elevation in BPA dose, the mRNAs of methyltransferases (Dnmt1, Dnmt3a, and Dnmt3b) were gradually upregulated. The mechanism was related to the activity of TLR4/NF-κB and PI3K/Akt/mTOR signaling pathways and the enhancement of Foxp3 DNA methylation. Our results, collectively, provided a new view for studying the mechanisms underlying BPA exposure-induced immune dysfunction. Investigation of the regulatory mechanisms of DNA methylation in the abnormal Th immune response caused by BPA exposure could help reveal the causes and molecular mechanisms underlying the high incidence of allergic diseases in children in recent years.

Chinese children are exposed to broad environmental risks ranging from well-known hazards, such as pesticides and heavy metals, to emerging threats including many new man-made chemicals. Although anecdotal evidence suggests that the exposure levels in Chinese children are substantially higher than those of children in developed countries, a systematic assessment is lacking. Further, while these exposures have been linked to a variety of childhood diseases, such as respiratory, endocrine, neurological, behavioral, and malignant disorders, the magnitude of the associations is often unclear. This review provides a current epidemiologic overview of commonly reported environmental contaminants and their potential impact on children's health in China. We found that despite a large volume of studies on various topics, there is a need for more high-quality research and better-coordinated regional and national data collection. Moreover, prevention of such diseases will depend not only on training of environmental health professionals and enhanced research programs, but also on public education, legislation, and networking.

Endocrine-disrupting chemicals may play a role in adiposity development during childhood. Until now literature in this scope suffers from methodologic limitations in exposure assessment using one or few urine samples and missing assessment during the infancy period.

We investigated the associations between early-life exposure to quickly metabolized chemicals and post-natal growth, relying on repeated within-subject urine collections over pregnancy and infancy.

We studied the associations of four phenols, four parabens, seven phthalates, and one nonphthalate plasticizer from weekly pooled urine samples collected from the mother during second and third trimesters (median 18 and 34 gestational weeks, respectively) and infant at 2 and 12 months of age, and child growth until 36 months. We relied on repeated measures of height, weight and head circumference from study visits and the child health booklet to predict growth outcomes at 3 and 36 months using the Jenss-Bayley nonlinear mixed model. We assessed associations with individual chemicals using adjusted linear regression and mixtures of chemicals using a Bayesian kernel machine regression model.

The unipollutant analysis revealed few associations. Bisphenol S (BPS) at second trimester was positively associated with all infant growth parameters at 3 and 36 months, with similar patterns between exposure at third trimester and all infant growth parameters at 3 months. Mono-n-butyl phthalate (MnBP) at 12 months was positively associated with body mass index (BMI), weight, and head circumference at 36 months. Mixture analysis revealed positive associations between exposure at 12 months and BMI and weight at 36 months, with MnBP showing the highest effect size within the mixture.

This study suggests that exposure in early infancy may be associated with increased weight and BMI in early childhood, which are risk factors of obesity in later life. Furthermore, this study highlighted the impact of BPS, a compound replacing bisphenol A, which has never been studied in this context. https://doi.org/10.1289/EHP13644.

Bisphenol A (BPA) is known as an obesogenic endocrine disruptor. Bisphenol S (BPS) and F (BPF) are substitutes that have recently replaced BPA.

To investigate the relationships of urinary bisphenols (BPA, BPS and BPF) with adiposity measurements (obesity, BMI z-score, and fat mass), serum adipokine levels (adiponectin and leptin), and adiponectin/leptin ratio (A/L ratio) in 6- and 8-year-old children.

A total of 561 children who participated in the Environment and Development of Children cohort (482 and 516 children visited at age 6 and 8, respectively) at Seoul National University Children's Hospital during 2015-2019 were included. Urinary BPA levels were log-transformed. BPS levels were categorized into three groups (non-detected, lower-half, and higher-half of detected), and BPF levels were classified into two groups (non-detected and detected).

The urinary BPS higher-half group had a higher BMI z-score (β = 0.160, P= 0.044), higher fat mass (β = 0.104, P< 0.001), lower adiponectin concentration (β =- 0.069, P< 0.001), higher leptin concentration (β = 0.360, P< 0.001), and lower A/L ratio (β =- 0.428, P< 0.001) compared with the non-detected group. The urinary BPF-detected group had a higher fat mass (β = 0.074, P< 0.001), lower adiponectin concentration (β =- 0.069, P< 0.001), higher leptin concentration (β = 0.360, P< 0.001), and lower A/L ratio (β =- 0.428, P< 0.001) compared with the non-detected group. The BPA levels showed no consistent associations with outcomes, except for isolated associations of BPA at age 6 with a higher BMI z-score at age 6 (P= 0.016) and leptin at age 8 (P= 0.021).

Increased exposure to BPS and BPF is associated with higher fat mass and leptin concentration, lower serum adiponectin, and lower A/L ratio in children. These findings suggest potential adverse effects of BPA substitutes on adiposity and adipokines. No consistent association of BPA exposure with outcomes could be partly explained by the decreasing BPA levels over time.

Obesity represents an important public health concern, being one of the leading causes of death worldwide. It is a multifactorial disease with many underlying intertwined causes, including genetic, environmental and behavioral factors. Notably, metabolism-disrupting chemicals (MDCs) can alter the set point control of metabolism, affecting the development and function of the adipose tissue. Epidemiological studies have reported associations between human exposure to MDCs and several altered metabolic endpoints. It is also noteworthy that sex and gender represent important risk factors in the development of obesity. Different sex-related biological and physiological characteristics influence individual susceptibility, whereas gender represents a critical component in determining the different exposure scenarios. Although some advancements in the treatment of obesity have been achieved in preclinical and clinical studies, the obesity pandemic continues to increase worldwide. The present study performed a systematic review of recent studies considering the effects of MDCs on obesity, with a specific focus on sex- and gender-related responses. This review highlighted that MDCs could differently affect men and women at different stages of life even though the number of studies evaluating the association between obesity and MDC exposure in relation to sex and gender is still limited. This evidence should urge researchers to carry out studies considering sex and gender differences. This is essential for developing sex-/gender-tailored prevention strategies to improve public health policies and reduce exposure.

Excess body weight constitutes one of the major health challenges for societies and healthcare systems worldwide. Besides the type of diet, calorie intake and the lack of physical exercise, recent data have highlighted a possible association between endocrine-disrupting chemicals (EDCs), such as bisphenol A, phthalates and their analogs, and obesity. EDCs represent a heterogeneous group of chemicals that may influence the hormonal regulation of body mass and adipose tissue morphology. Based on the available data from mechanistic, animal and epidemiological studies including meta-analyses, the weight of evidence points towards the contribution of EDCs to the development of obesity, associated disorders and obesity-related adipose tissue dysfunction by (1) impacting adipogenesis; (2) modulating epigenetic pathways during development, enhancing susceptibility to obesity; (3) influencing neuroendocrine signals responsible for appetite and satiety; (4) promoting a proinflammatory milieu in adipose tissue and inducing a state of chronic subclinical inflammation; (5) dysregulating gut microbiome and immune homeostasis; and (6) inducing dysfunction in thermogenic adipose tissue. Critical periods of exposure to obesogenic EDCs are the prenatal, neonatal, pubertal and reproductive periods. Interestingly, EDCs even at low doses may promote epigenetic transgenerational inheritance of adult obesity in subsequent generations. The aim of this review is to summarize the available evidence on the role of obesogenic EDCs, specifically BPA and phthalate plasticizers, in the development of obesity, taking into account in vitro, animal and epidemiologic studies; discuss mechanisms linking EDCs to obesity; analyze the effects of EDCs on obesity in critical chronic periods of exposure; and present interesting perspectives, challenges and preventive measures in this research area.

Bisphenol S (BPS) and bisphenol F (BPF) are increasingly used to replace bisphenol A (BPA), an endocrine-disrupting chemical with putative obesogenic properties; whether and how BPS and BPF affect adiposity in humans remains to be determined. Therefore, we examined the association of BPA, BPS， and BPF with body composition among US adults. We included 1787 participants aged 20-59 years old in the National Health and Nutrition Examination Survey 2013-2016 who had information on urinary BPA, BPS, and BPF concentrations, and body composition measured using dual-energy x-ray absorptiometry. After full adjustment for potential confounders in linear regression models, BPA was significantly associated with the % body fat of the whole body, arm, and leg, with the β (95% CI) for the highest quartile vs. the lowest quartile of 1.34 (95%CI [0.11, 2.58], P = 0.03), 1.60 (95%CI [0.20, 3.00], P = 0.03), and 1.63 (95%CI [0.24, 3.02], P = 0.02), respectively. No association between BPA and lean mass was found. For BPS, significant associations were found for % body fat of the whole body (β [95% CI] = 1.42 [0.49, 2.36], P = 0.004), trunk (β[95% CI] = 1.92 [0.86, 2.97], P = 0.001), and arm (β [95% CI] = 1.60 [0.49, 2.70], P = 0.01), as well as lean mass of the whole body (β [95% CI] = 2610.6 [1324.3, 3896.8], P < 0.001), trunk (β [95% CI] = 1467.0 [745.3, 2188.7], P < 0.001), arm (β [95% CI] = 113.4 [10.3, 216.5], P = 0.03), and leg (β [95% CI] = 431.5 [219.6, 643.4], P < 0.001), comparing the third quartile vs. the lowest quartile. No significant association was observed between BPF and % body fat and lean mass. Results suggest that higher BPA levels were significantly associated with greater % body fat of the whole body and limbs, and there was suggestive evidence that BPS levels were associated with both % body fat and lean mass of the whole body and body parts in a nonmonotonic relationship.

Bisphenol A (BPA) and its structural analogs (bisphenol S (BPS) and bisphenol F (BPF)) are widely consumed endocrine disrupting chemicals that may contribute to the etiology of obesity. To date, few studies have directly investigated the sex-related associations between bisphenols and body fat distribution in adults. In this study, we included 2669 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 to evaluate and compare sex-specific differences of the associations of BPA, BPS, and BPF with body fat distribution. We found that there were significant positive correlations between BPS and body fat indices (STFAT [adjustedβ=1.94, 95% CI: (0.24, 3.64)], TAF [0.18 (0.04, 0.32)], SAT [0.15 (0.03, 0.27)], android fat mass [0.20 (0.004, 0.40)], BMI [1.63 (0.61, 2.65)], and WC [3.19 (0.64, 5.73)] in the highest quartiles of BPS), but not in BPA and BPF. Stratified analyses suggested that the significant associations of BPS with body fat indices were stronger in women than men (STFAT [adjustedβ=3.75, 95% CI: (1.04, 6.45) vs. adjustedβ=-0.06, 95% CI: (-2.23, 2.11), P for interaction < 0.001], TAF [ 0.32 (0.09, 0.54) vs. 0.01 (-0.17, 0.19), P for interaction < 0.001], SAT [0.27 (0.09, 0.45) vs. 0.01 (-0.14, 0.16), P for interaction < 0.001], android fat mass [0.41 (0.12, 0.71) vs. -0.02 (-0.28, 0.24), P for interaction < 0.001], gynoid fat mass [0.56 (0.11, 1.01) vs. -0.05 (-0.41, 0.31), P for interaction = 0.002], BMI [2.76 (1.08, 4.44) vs. 0.47 (-0.80, 1.74), P for interaction < 0.001], and WC [5.51 (1.44, 9.58) vs. 0.61 (-2.67, 3.88), P for interaction < 0.001]), and positive associations between BPS with fat distribution were also observed in non-smoking women. Our study indicated that in women, higher concentration of urinary BPS was associated with increased body fat accumulation, except for visceral adipose tissue mass. These findings emphasize the role of environmental BPS exposure in the increasing fat deposits, and confirm the need for more prospective cohort studies on a sex-specific manner.

Bisphenol S (BPS) exposure has been implied epidemiologically to increase obesity risk, but the underlying mechanism is unclear. Here, we propose that BPS exposure at an environmentally relevant dose aggravates diet-induced obesity in female mice by inducing brown adipose tissue (BAT) whitening. We explored the underlying mechanism by which KDM5A-associated demethylation of the trimethylation of lysine 4 on histone H3 (H3K4me3) in thermogenic genes is overactivated in BAT upon BPS exposure, leading to the reduced expression of thermogenic genes. Further studies have suggested that BPS activates KDM5A transcription in BAT by binding to glucocorticoid receptor (GR) in an estrogen-dependent manner. Estrogen-estrogen receptors facilitate the accessibility of the KDM5A gene promoter to BPS-activated GR by recruiting the activator protein 1 (AP-1) complex. These results indicate that BAT is another important target of BPS and that targeting KDM5A-related signals may serve as an approach to counteract the BPS-induced susceptivity to obesity.

Prenatal exposure to endocrine-disrupting bisphenol A (BPA) shows a long-lasting programming effect on an organ's metabolic function and predisposes it to the risk of adult metabolic diseases. Although a reduced contaminant risk due to "BPA-free" exposure is proposed, limited data on a comparative assessment of gestational exposure to BPS and BPA and their effects on metaflammation in predisposing liver metabolic disease is reported. Pregnant Wistar rats were exposed to BPS and BPA (0.0, 0.4, 4.0 μg/kg bw) via gavage from gestational day 4 to 21, and effects were assessed in the 90 d male offspring. Prenatal BPS-exposed offspring showed a more obesogenic effect than BPA, including changes in body fat distribution, feed efficiency, and leptin signalling. The BPS exposure induced the adipocyte hypertrophy of visceral adipose to a greater extent than BPA. The adipose hypertrophy was augmented by tissue inflammation, endoplasmic reticulum (ER) stress, and apoptosis due to increased expression of pro-inflammatory (IL6, IL1β, CRP, COX2) cytokines, ER stress modulator (CHOP), and apoptotic effector (Caspase 3). The enlarged, stressed, inflamed adipocytes triggered de novo lipogenesis in the bisphenol-exposed offspring liver due to increased expression of cholesterol and lipid biogenesis mediators (srebf1, fasn, acaca, PPARα) concomitant with elevated triacylglycerol (TG) and cholesterol (TC), resulted in impaired hepatic clearance of lipids. The lipogenic effects were also promoted by increased expression of HSD11β1. BPS exposure increased absolute liver weight, discoloration, altered liver lobes more than in BPA. Liver histology showed numerous lipid droplets, and hepatocyte ballooning, upregulated ADRP expression, an increased expression of pro-inflammatory mediators (IL6, CRP, IL1β, TNFα, COX2), enhanced lipid peroxidation in the BPS-exposed offspring's liver suggest altered metaflammation leads to microvesicular steatosis. Overall, gestational BPS exposure demonstrated a higher disruption in metabolic changes than BPA, involving excess adiposity, liver fat, inflammation, and predisposition to steatosis in the adult male offspring.

Childhood exposure to endocrine-disrupting chemicals (EDCs), either alone or in mixtures, may affect metabolic outcomes, yet existing evidence remains inconclusive. In our study of 372 adolescents from the Flemish Environment and Health Study (FLEHS IV, 2017-2018), we measured 40 known and suspected EDCs and assessed metabolic outcomes, including body mass index z-score (zBMI), abdominal obesity (AO), total cholesterol (TC), and triglycerides (TG). We applied Bayesian kernel machine regression (BKMR) and Bayesian penalized horseshoe regression for variable selection and then built multivariate generalized propensity score (mvGPS) models to provide an overview of the effects of selected EDCs on metabolic outcomes. As a result, BKMR and horseshoe together identified five EDCs associated with zBMI, three with AO, three with TC, and five with TG. Through mvGPS analysis, monoiso-butyl phthalate (MIBP), polychlorinated biphenyl (PCB-170), and hexachlorobenzene (HCB) each showed an inverse association with zBMI, as did PCB-170 with AO. Copper (Cu) was associated with higher TC and TG, except in boys where it was linked to lower TG. Additionally, monoethyl phthalate (MEP) and monobenzyl phthalate (MBzP) were associated with higher TG. To conclude, our findings support the association between certain chemicals (Cu, MEP, and MBzP) and elevated lipid levels, aligning with prior studies. Further investigation is needed for sex-specific effects.

Bisphenol A (BPA; 4,4'-isopropylidenediphenol) is a well-known endocrine disruptor. Most human exposure to BPA occurs through the consumption of BPA-contaminated foods. Cardiovascular or cardiometabolic diseases such as diabetes, obesity, hypertension, acute kidney disease, chronic kidney disease, and heart failure are the leading causes of death worldwide. Positive associations have been reported between blood or urinary BPA levels and cardiovascular or cardiometabolic diseases. BPA also induces disorders or dysfunctions in the tissues associated with these diseases through various cell signaling pathways. This review highlights the literature elucidating the relationship between BPA and various cardiovascular or cardiometabolic diseases and the potential mechanisms underlying BPA-mediated disorders or dysfunctions in tissues such as blood vessels, skeletal muscle, adipose tissue, liver, pancreas, kidney, and heart that are associated with these diseases.

Bisphenol A (BPA) and its substitutes are widely used in daily life. Animal and cell line experiments have confirmed the effects of bisphenols on oxidative stress and inflammation. However, current population evidence for the effects of BPA alternatives, such as bisphenol F (BPF) and bisphenol S (BPS), on oxidative stress and inflammation is still sparse. Based on the National Health and Nutrition Examination Survey 2013-2016 data, our study used linear regression, weighted quantile sum model, and Bayesian kernel machine regression model to evaluate the effects of BPA, BPS, and BPF alone and in combination on oxidative stress (serum total bilirubin, and iron) and inflammation (alkaline phosphatase, C-reactive protein, γ-glutamyl transferase ferritin, neutrophil count, lymphocyte count, and neutrophil-to-lymphocyte ratio) markers. On this basis, the possible roles of oxidative stress and inflammation in obesity, which is associated with exposure to bisphenols (BPs), were initially explored. Based on the different covariates selected, a total of 3039 and 2258 participants were included in our study for models 1 and 2, respectively; the median age of participants was 48 years, and 48.7 % were male. Based on all models, our results showed that exposure to BPs alone or in combination was associated with downregulation of serum total bilirubin. Urinary BPF concentration was specifically associated with the neutrophil-to-lymphocyte ratio. Serum total bilirubin may play a role in the association between obesity and BP mixture exposure. Upregulation of the neutrophil-to-lymphocyte ratio was not associated with obesity. In conclusion, our study found that single or combined exposure to BPs, as measured in urine, may be associated with changes in oxidative stress and inflammatory markers, and a decrease in serum total bilirubin may play a mediating role in BP-induced obesity.

The association between Insulin resistance, a global health issue, and endocrine disruptors (EDCs), chemicals interfering with the endocrine system, has sparked concern in the scientific community. This article provides a comprehensive review of the existing literature regarding the intricate relationship between EDCs and insulin resistance. Phthalates, commonly found in consumer products, are well-established EDCs with documented effects on insulin-signaling pathways and metabolic processes. Epidemiological studies have connected phthalate exposure to an increased risk of type 2 diabetes mellitus (T2DM). Perfluoroalkyl substances (PFAS), persistent synthetic compounds, have shown inconsistent associations with T2DM in epidemiological research. However, studies suggest that PFAS may influence insulin resistance and overall metabolic health, with varying effects depending on specific PFAS molecules and study populations. Bisphenol A (BPA), found in plastics and resins, has emerged as a concern for glucose regulation and insulin resistance. Research has linked BPA exposure to T2DM, altered insulin release, obesity, and changes in the mass and function of insulin-secreting β-cells. Triclosan, an antibacterial agent in personal care products, exhibits gender-specific associations with T2DM risk. It may impact gut microbiota, thyroid hormones, obesity, and inflammation, raising concerns about its effects on metabolic health. Furthermore, environmental EDCs like polycyclic aromatic hydrocarbons, pesticides, and heavy metals have demonstrated associations with T2DM, insulin resistance, hypertension, and obesity. Occupational exposure to specific pesticides and heavy metals has been linked to metabolic abnormalities.

Prenatal exposure to mixtures of endocrine disrupting chemicals (EDC) has the potential to disrupt human metabolism. Prenatal periods are especially sensitive as many developmental processes are regulated by hormones. Prenatal exposure to EDCs has inconsistently been associated with children's body mass index (BMI) and obesity. The objective of this study was to investigate if prenatal exposure to a mixture of EDCs was associated with children's BMI and overweight (ISO-BMI ≥ 25) at 5.5 years of age, and if there were sex-specific effects.

A total of 1,105 mother-child pairs with complete data on prenatal EDCs concentrations (e.g., phthalates, non-phthalate plasticizers, phenols, PAH, pesticides, PFAS, organochlorine pesticides, and PCBs), children's measured height and weight, and selected covariates in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study were included in this analysis. The mixture effect of EDCs with children's BMI and overweight was assessed using WQS regression with 100 repeated holdouts. A positively associated WQS index with higher BMI and odds of overweight was derived. Models with interaction term and stratified weights by sex was applied in order to evaluate sex-specific associations.

A significant WQS*sex interaction term was identified and associations for boys and girls were in opposite directions. Higher prenatal exposure to a mixture of EDCs was associated with lower BMI (Mean β = -0.19, 95%CI: -0.40, 0.01) and lower odds of overweight (Mean OR = 0.72, 95%CI: 0.48, 1.04) among girls with borderline significance. However, the association among boys did not reach statistical significance. Among girls, the possible chemicals of concern were MEP, 2-OHPH, BPF, BPS, DPP and PFNA.

Prenatal exposure to a mixture of EDCs was associated with lower BMI and overweight among girls, and non-significant associations among boys. Chemicals of concern for girls included phthalates, non-phthalate plasticizers, bisphenols, PAHs, and PFAS.

A growing number of studies link the increase in overweight/obesity worldwide to exposure to certain environmental chemical pollutants that display obesogenic activity (obesogens). Since exposure to obesogens during the first stages of life has been shown to have a more intense and pronounced effect at lower doses, it is imperative to study their possible effects in childhood. The objective here was to study the association of Bisphenol A (BPA) and 11 BPA analogs in children, using three biological matrices (nails, saliva and urine), and overweight and obesity (n = 160).

In this case-control study, 59 overweight/obese children and 101 controls were included. The measuring of Bisphenols in the matrices was carried out by ultra-high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-MS/MS). Logistic regression was used to study the association between overweight/obesity and Bisphenol exposure.

The results suggested that BPF in nails is associated with overweight/ obesity in children (OR:4.87; p = 0.020). In saliva, however, the highest detected concentrations of BPAF presented an inverse association (OR: 0.06; p = 0.010) with overweight/obesity. No associations of statistical significance were detected between exposure to BPA or its other analogs and overweight/obesity in any of the biological matrices.

Exposure to bisphenol analogues can occur in several ways throughout the food production chain, with their presence at higher concentrations representing a risk to human health. This study aimed to develop effective analytical methods to simultaneously quantify BPA and fifteen bisphenol analogues (i.e., bisphenol AF, bisphenol AP, bisphenol B, bisphenol BP, bisphenol C, bisphenol E, bisphenol F, bisphenol G, bisphenol M, bisphenol P, bisphenol PH, bisphenol S, bisphenol Z, bisphenol TMC, and tetramethyl bisphenol F) present in canned foods and beverages. Samples of foods and beverages available in the Swiss and EU markets (n = 22), including canned pineapples, ravioli, and beer, were prepared and analyzed using QuEChERS GC-MS. The quantification method was compared to a QuEChERS LC-MS/MS analysis. This allowed for the selective and efficient simultaneous quantitative analysis of bisphenol analogues. Quantities of these analogues were present in 20 of the 22 samples tested, with the most frequent analytes at higher concentrations: BPA and BPS were discovered in 78% and 48% of cases, respectively. The study demonstrates the robustness of QuEChERS GC-MS for determining low quantities of bisphenol analogues in canned foods. However, further studies are necessary to achieve full knowledge of the extent of bisphenol contamination in the food production chain and its associated toxicity.

The prevalence of obesity, a condition associated with increased health risks, has risen significantly over the past several decades. Although obesity develops from energy imbalance, its etiology involves a multitude of other factors. One of these factors are endocrine disruptors, or "obesogens", when in reference to obesity. Bisphenol A (BPA), a known endocrine disruptor used in plastic materials, has recently been described as an environmental obesogen. Although BPA-free products are becoming more common now than in the past, concerns still remain about the obesogenic properties of the compounds that replace it, namely Bisphenol S (BPS), Bisphenol F (BPF), and Bisphenol AF (BPAF). The purpose of this review is to investigate the relationship between BPA substitutes and obesity. Literature on the relationship between BPA substitutes and obesity was identified through PubMed and Google Scholar, utilizing the search terms "BPA substitutes", "bisphenol analogues", "BPS", "BPF", "BPAF", "obesity", "obesogens", "adipogenesis", "PPARγ", and "adipocyte differentiation". Various population-based studies were assessed to gain a better understanding of the epidemiology, which revealed evidence that BPA substitutes may act as obesogens at the pathophysiological level. Additional studies were assessed to explore the potential mechanisms by which these compounds act as obesogens. For BPS, these mechanisms include Peroxisome proliferator-activated receptor gamma (PPARγ) activation, potentiation of high-fat diet induced weight-gain, and stimulation of adipocyte hypertrophy and adipose depot composition. For BPF and BPAF, the evidence is more inconclusive. Given the current understanding of these compounds, there is sufficient concern about exposures. Thus, further research needs to be conducted on the relationship of BPA substitutes to obesity to inform on the potential public health measures that can be implemented to minimize exposures.

Epidemiologic evidence supports a positive association between ultraprocessed food (UPF) consumption and body mass index. This has led to recommendations to avoid UPFs despite very limited evidence establishing causality. Many mechanisms have been proposed, and this review critically aimed to evaluate selected possibilities for specificity, clarity, and consistency related to food choice (i.e., low cost, shelf-life, food packaging, hyperpalatability, and stimulation of hunger/suppression of fullness); food composition (i.e., macronutrients, food texture, added sugar, fat and salt, energy density, low-calorie sweeteners, and additives); and digestive processes (i.e., oral processing/eating rate, gastric emptying time, gastrointestinal transit time, and microbiome). For some purported mechanisms (e.g., fiber content, texture, gastric emptying, and intestinal transit time), data directly contrasting the effects of UPF and non-UPF intake on the indices of appetite, food intake, and adiposity are available and do not support a unique contribution of UPFs. In other instances, data are not available (e.g., microbiome and food additives) or are insufficient (e.g., packaging, food cost, shelf-life, macronutrient intake, and appetite stimulation) to judge the benefits versus the risks of UPF avoidance. There are yet other evoked mechanisms in which the preponderance of evidence indicates ingredients in UPFs actually moderate body weight (e.g., low-calorie sweetener use for weight management; beverage consumption as it dilutes energy density; and higher fat content because it reduces glycemic responses). Because avoidance of UPFs holds potential adverse effects (e.g., reduced diet quality, increased risk of food poisoning, and food wastage), it is imprudent to make recommendations regarding their role in diets before causality and plausible mechanisms have been verified.

Environmental bisphenol compounds like bisphenol F (BPF) are endocrine-disrupting chemicals (EDCs) affecting adipose and classical endocrine systems. Genetic factors that influence EDC exposure outcomes are poorly understood and are unaccounted variables that may contribute to the large range of reported outcomes in the human population. We previously demonstrated that BPF exposure increased body growth and adiposity in male N/NIH heterogeneous stock (HS) rats, a genetically heterogeneous outbred population. We hypothesize that the founder strains of the HS rat exhibit EDC effects that were strain- and sex-dependent. Weanling littermate pairs of male and female ACI, BN, BUF, F344, M520, and WKY rats randomly received either vehicle (0.1% EtOH) or 1.125 mg BPF/l in 0.1% EtOH for 10 weeks in drinking water. Body weight and fluid intake were measured weekly, metabolic parameters were assessed, and blood and tissues were collected. BPF increased thyroid weight in ACI males, thymus and kidney weight in BUF females, adrenal weight in WKY males, and possibly increased pituitary weight in BN males. BUF females also developed a disruption in activity and metabolic rate with BPF exposure. These sex- and strain-specific exposure outcomes illustrate that HS rat founders possess diverse bisphenol-exposure risk alleles and suggest that BPF exposure may intensify inherent organ system dysfunction existing in the HS rat founders. We propose that the HS rat will be an invaluable model for dissecting gene EDC interactions on health.

Plastic pollution breaks a planetary boundary threatening wildlife and humans through its physical and chemical effects. Of the latter, the release of endocrine disrupting chemicals (EDCs) has consequences on the prevalence of human diseases related to the endocrine system. Bisphenols (BPs) and phthalates are two groups of EDCs commonly found in plastics that migrate into the environment and make low-dose human exposure ubiquitous. Here we review epidemiological, animal, and cellular studies linking exposure to BPs and phthalates to altered glucose regulation, with emphasis on the role of pancreatic β-cells. Epidemiological studies indicate that exposure to BPs and phthalates is associated with diabetes mellitus. Studies in animal models indicate that treatment with doses within the range of human exposure decreases insulin sensitivity and glucose tolerance, induces dyslipidemia, and modifies functional β-cell mass and serum levels of insulin, leptin, and adiponectin. These studies reveal that disruption of β-cell physiology by EDCs plays a key role in impairing glucose homeostasis by altering the mechanisms used by β-cells to adapt to metabolic stress such as chronic nutrient excess. Studies at the cellular level demonstrate that BPs and phthalates modify the same biochemical pathways involved in adaptation to chronic excess fuel. These include changes in insulin biosynthesis and secretion, electrical activity, expression of key genes, and mitochondrial function. The data summarized here indicate that BPs and phthalates are important risk factors for diabetes mellitus and support a global effort to decrease plastic pollution and human exposure to EDCs.

Neonicotinoid insecticides (NEOs) are emerging synthetic insecticides used in various pest management regimens worldwide. Toxicology studies have indicated the obesogenic potential of NEOs, but their associations with adiposity measures are largely unknown.

We aimed to assess urinary levels of NEOs/metabolites and their associations with children's adiposity measures, and to further investigate the potential role of oxidative stress.

This study included 380 children who participated in the 7th year's follow-up of the Laizhou Wan Birth Cohort in northern China. Urinary levels of seven NEOs and two metabolites and a biomarker of lipid peroxidation named 8-iso-prostaglandin-F2α (8-iso-PGF2α) were detected. A total of nine indicators of adiposity were measured. Body mass index (BMI) z-score ≥85th percentile was defined as overweight/obesity, and waist-to-height ratio (WHtR) ≥0.5 was considered as abdominal obesity. Multiple linear regression, binary logistic regression and mediation analysis were performed.

Six NEOs [imidacloprid (IMI, 99.7%), clothianidin (CLO, 98.9%), dinotefuran (DIN, 97.6%), thiamethoxam (THM, 95.5%), acetamiprid (ACE, 82.9%), thiacloprid (THD, 77.6%)] and two metabolites [N-desmethyl-acetamiprid (N-DMA, 100.0%), 6-chloronicotinic acid (6-CINA, 97.9%)] exhibited high detection rates. Multiple linear regressions showed positive associations of waist circumference with urinary levels of IMI and THM, of WHtR with IMI and THM levels, and of body fat percentage with 6-CINA levels. In contrast, exposure to N-DMA was negatively associated with body fat percentage and fat mass index. Binary logistic regressions further revealed that higher IMI levels were associated with overweight/obesity (OR = 1.556, 95% CI: 1.100, 2.201) and abdominal obesity (OR = 1.478, 95% CI: 1.078, 2.026) in children. 8-iso-PGF2α demonstrated 27.92%, 69.52% and 35.37% mediating effects in the positive associations of IMI, THD and THM with WHtR, respectively. Sex modified the associations of DIN with body fat mass (p_int = 0.032), body fat percentage (p_int = 0.009), fat mass index (p_int = 0.037) and the overweight/obesity rate (p_int = 0.046), with negative associations in girls and nonsignificant positive associations in boys.

School-age children in northern China were widely exposed to NEOs/metabolites. Urinary levels of NEOs/metabolites were associated with adiposity measures through the mediating role of 8-iso-PGF2α. These associations were mixed, and a sex-specific effect might exist.

Bisphenol A (BPA) substitutes, such as bisphenol S (BPS) and bisphenol AF (BPAF), are increasingly used due to restrictions on BPA usage, a known endocrine disrupting chemical and putative obesogen. However, little is known about the obesogenic effects of exposure to BPA substitutes in children. A total of 426 children aged 7 years old originally recruited from Laizhou Wan Birth Cohort in Shandong, China, during 2010-2013 participated in the 2019-2020 survey. Urinary BPA and its substitutes including BPS, BPAF, bisphenol B (BPB), bisphenol AP (BPAP), bisphenol Z (BPZ), and bisphenol P (BPP) were determined. Anthropometric measures including height, weight, waist circumference, and body fat percentage were assessed, and overweight/obesity was defined as BMI z-score ≥ 85th percentile. Linear and logistic regressions were used on continuous and binary obesity measures, respectively, and weighted quantile sum (WQS) regression was further used to estimate the mixture effects of exposure to diverse bisphenols, and sex-stratified analysis was performed. BPA substitutes were widely detected (> 75%) in children's urine samples. A positive association with obesity measures was consistently observed for urinary BPS and BPAF, i.e., BMI z-score, waist circumference, and overweight/obesity. Further analysis from the WQS regression model demonstrated a positive association between bisphenol mixtures and all measures of obesity, with BPAF contributing the greatest weighing to the observed associations. Sex difference might exist as the positive associations were only significant in boys. No significant association was found between obesity and BPA or other BPA substitutes. Our study adds to mounting evidence that BPA substitutes BPS and BPAF are linked to obesity in children, especially in boys. Further longitudinal studies with larger sample size with continued biomonitoring these chemicals and their obesogenic effects are necessary.

Emerging bisphenol S analogues (BPSs) have gained their application perspectives to replace bisphenol A (BPA) and BPA analogues (BPAs). However, the extent of human exposure and potential health risk from BPSs is rarely known yet. We hypothesized that children living in Shantou, China, a well-known e-waste recycling city, may expose to emerging BPSs together with BPA and BPAs. In this study, BPA, six commonly used BPAs and 11 emerging BPSs were determined simultaneously in 240 urine samples collected from children residing in Shantou. BPA, BPS, bisphenol F, bisphenol AF and three BPSs of 2,4'-bis(hydroxyphenyl)sulfone, 4-((4-(allyloxy)phenyl)sulfonyl)phenol and diphenylsulfone (DPS) were the urinary predominant bisphenols with detection frequencies of 67-100% in the children. BPA was found at the highest median concentration (3.36 µg/g creatinine) followed by BPS (0.313) and DPS (0.187). It is interesting to find that the girls and children in the younger group (2 ≤ age < 5) had consistently higher concentrations of the seven dominant bisphenols than the boys and these of the older group (5 ≤ age ≤ 10), respectively. The children with under/overweight suffered higher burdens of bisphenol exposure based on medians of estimated daily intakes. Association analysis results indicated that the Shantou children exposed themselves to multiple BPSs along with BPA and BPAs from assumed consumer products and/or contaminated environments.