Bisphenol A (BPA) is a representative endocrine disrupting compound used in a vast array of consumer products, and are being frequently substituted by its analogues, bisphenol S (BPS) and bisphenol F (BPF). We aimed to examine the association between urinary bisphenol levels with obesity and lipid profiles in the general population to comprehensively evaluate its potential of metabolic disturbance. A representative sample of 1046 US adults from the National Health and Nutrition Examination Survey (2013–2016) and 3268 Korean adults from the Korean National Environmental Health Survey (2015–2017) was analyzed. We examined the exposure levels of bisphenols and determined their associations with obesity, high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels, and hypercholesterolemia prevalence through multiple linear, and binary/ordinal logistic regression models. In both populations, high BPA levels (lowest tertile vs. 2nd, 3rd tertiles) showed corresponding associations with lipid profile and obesity. BPA levels were associated with decreased HDL-C levels (Q3: β = −0.053, p = 0.08 (US); Q2: β = −0.030, p-0.03), increased TG levels (Q3: β = 0.121, p = 0.029 (US); Q3: β = 0.089, p = 0.021, and higher odds for obesity (Q3: OR = 1.58, 95% CI: 1.06, 2.35 (US); Q3: OR = 1.41, 95% CI: 1.11, 1.78). Higher BPS levels were positively associated with obesity status, especially in US men (Q2: OR = 1.84, 95% CI: 1.15, 2.96) and Korean women (Q3: OR = 1.27, 95% CI: 0.99, 1.64). A significant decrease in HDL-C (Q3: β = −0.088, p = 0.01) and elevated odds for obesity at higher BPF levels (Q3: OR = 1.60, 95% CI: 1.00, 2.56) was observed in US women. The findings of our study indicate that BPA and its analogues, BPS and BPF, are associated with lipid metabolism disorders in addition to obesity in adults. Given the increase in exposure to BPA alternatives, continuous biomonitoring, and further investigation of their health effects through prospective cohort studies are warranted.

Environmental obesogens contributed significantly to the obesity prevalence. Recently, antibiotics joined the list of environmental obesogens, while the underlying mechanisms remained to be explored. In the present study, effects of erythromycin (ERY), one widely used macrolide antibiotic, were measured on C. elegans to investigate the obesogenic mechanism. Results showed that ERY at 0.1 μg/L significantly increased the fat content by 17.4% more than the control and also stimulated triacylglycerol (TAG) levels by 25.7% more than the control. Regarding the obesogenic mechanisms, ERY provoked over-eating by stimulation on the pharyngeal pumping and reduction on the satiety quiescence percentage and duration. Such effects were resulted from stimulation on the neurotransmitters including serotonin (5-HT), dopamine (DA) and acetylcholine (ACh). The nervous responses involved the up-regulation of Gsα (e.g., ser-7, gsa-1, acy-1 and kin-2) signaling pathway and the down-regulation of TGFβ (daf-7) but not via cGMP-dependent regulations (e.g., egl-4). Moreover, ERY stimulated the activities of fatty acid synthase (FAS) and glycerol-3-phosphateacyl transferases (GPAT) that catalyze lipogenesis, while ERY inhibited those of acyl-CoA synthetase (ACS), carnitine palmitoyl transferase (CPT) and acyl-CoA oxidase (ACO) that catalyze lipolysis. The unbalance between lipogenesis and lipolysis resulted in the fat accumulation which was consistent with up-regulation on mgl-1 and mgl-3 which are the down-steam of TGFβ regulation. Such consistence supported the close connection between nervous regulation and lipid metabolism. In addition, ERY also disturbed insulin which connects lipid with glucose in metabolism.

The influence of pollutants on metabolic diseases such as type 2 diabetes mellitus is an emerging field in environmental medicine. Here, we explored the effects of a low-dose endosulfan sulfate (ES), a major metabolite of the pesticide endosulfan and a bio-persistent contaminant detected in environmental and human samples, on the progress of obesity and metabolic disorders. Pregnant CD-1 mice were given ES from gestational day 6 to postnatal day 21 (short-term). After weaning, male pups of exposed dams were provided with a low-fat or a high-fat diet (LFD or HFD) and assessed after an additional 12 weeks. At the same time, one group of male pups continuously received ES (long-term). Treatment with low-dose ES, short or long-term, alleviated the development of obesity and accumulation of hepatic triglycerides induced by HFD. Analysis of gene expression, metabolic profile and gut microbiome indicates that ES treatment inhibits adipogenesis induced by HFD due to enhanced lipid catabolism, fatty acid oxidation and disturbance of gut microbiota composition. However, impaired glucose and insulin homeostasis were still conserved in HFD-fed mice exposed to ES. Furthermore, ES treatment impaired glucose tolerance, affected hepatic gene expression, fatty acids composition and serum metabolic profile, as well as disturbed gut microbiota in LFD-fed mice. In conclusion, ES treatment at levels close to the accepted daily intake during fetal development directly impact glucose homeostasis, hepatic lipid metabolism, and gut microbiome dependent on the type of diet consumed. These findings provide a better understanding of the complex interactions of environmental pollutants and diet at early life stages also in the context of metabolic disease.

Perfluorooctanesulfonic acid (PFOS) is a persistent environmental contaminant previously found in consumer surfactants and industrial fire-fighting foams. PFOS has been widely implicated in metabolic dysfunction across the lifespan, including diabetes and obesity. However, the contributions of the embryonic environment to metabolic disease remain uncharacterized. This study seeks to identify perturbations in embryonic metabolism, pancreas development, and adiposity due to developmental and subchronic PFOS exposures and their persistence into later larval and juvenile periods. Zebrafish embryos were exposed to 16 or 32 μM PFOS developmentally (1–5 days post fertilization; dpf) or subchronically (1–15 dpf). Embryonic fatty acid and macronutrient concentrations and expression of peroxisome proliferator-activated receptor (PPAR) isoforms were quantified in embryos. Pancreatic islet morphometry was assessed at 15 and 30 dpf, and adiposity and fish behavior were assessed at 15 dpf. Concentrations of lauric (C12:0) and myristic (C14:0) saturated fatty acids were increased by PFOS at 4 dpf, and PPAR gene expression was reduced. Incidence of aberrant islet morphologies, principal islet areas, and adiposity were increased in 15 dpf larvae and 30 dpf juvenile fish. Together, these data suggest that the embryonic period is a susceptible window of metabolic programming in response to PFOS exposures, and that these early exposures alone can have persisting effects later in the lifecourse.

Tributyltin (TBT), an organotin compound once widely used in agriculture and industry, has been reported to induce obesity and endocrine disruption. Gut microbiota has a strong connection with the host’s physiology. Nevertheless, the influences of TBT exposure on gut microbiota and whether TBT-influenced gut microbiota is related to TBT-induced toxicity remain unclear. To fill these gaps, ICR (CD-1) mice were respectively exposed to TBT at NOEL (L-TBT) and tenfold NOEL (H-TBT) daily by gavage for 8 weeks in the current study. The results showed that TBT exposure significantly increased body weight as well as epididymal fat, and led to adipocyte hypertrophy, dyslipidemia and impaired glucose and insulin homeostasis in mice. Additionally, TBT exposure significantly decreased the levels of T4, T3 and testosterone in serum. Also of note, TBT exposure changed gut microbiota composition mainly by decreasing Bacteroidetes and increasing Firmicutes proportions. To confirm the role of gut microbiota in TBT-induced overweight and hormonal disorders, fecal microbiota transplantation was performed and the mice receiving gut microbiota from H-TBT mice had similar phenotypes with their donor mice including significant body weight and epididymal fat gain, glucose and insulin dysbiosis and hormonal disorders. These results suggested that gut microbiome altered by TBT exposure was involved in the TBT-induced increased body weight, impaired glucose and insulin homeostasis and endocrine disruption in mice, providing significant evidence and a novel perspective for better understanding the mechanism by which TBT induces toxicity.

Perchlorate is a pervasive, water-soluble contaminant that competitively inhibits the sodium/iodide symporter, reducing the available iodide for thyroid hormone synthesis. Insufficient iodide uptake can lead to hypothyroidism and metabolic syndromes. Because metabolism, obesity and non-alcoholic fatty liver disease (NAFLD) are tightly linked, we hypothesized that perchlorate would act as an obesogen and cause NAFLD via accumulation of lipids in liver of developing threespine stickleback (Gasterosteus aculeatus). We performed an upshift/downshift exposure regime (clean water to perchlorate treated water or perchlorate treated water to clean water) on stickleback embryos at two concentrations (30 mg/L and 100 mg/L) plus the control (0 mg/L) over the course of 305 days. Adult stickleback were euthanized, H&E stained and analyzed for liver morphology. Specifically, we counted the number of lipid droplets, and measured the area of each droplet and the total lipid area of a representative section of liver. We found that perchlorate treated fish had more and larger lipid droplets, and a larger percentage of lipid in their liver than control fish. These data indicate that perchlorate causes NAFLD and hepatic steatosis in stickleback at concentrations commonly found at contaminated sites. These data also indicate the potential of perchlorate to act as an obesogen. Future studies should investigate the obesogenic capacity of perchlorate by examining organ specific lipid accumulation and whether perchlorate induces these effects at concentrations commonly found in drinking water. Work is also needed to determine the mechanisms by which perchlorate induces lipid accumulation.

Decabromodiphenyl Ethane (DBDPE), a kind of new brominated flame retardants (NBFRs) used to replace DecaBDE, has been frequently detected in the environment and human samples. In this study, we explored its toxic effects on male mouse offspring after perinatal exposure to DBDPE. During the perinatal period, pregnant ICR mice were exposed to DBDPE (100 μg/kg body weight) via oral gavage. After weaning, male offspring were fed on a low-fat diet and a high-fat diet, respectively. We measured and recorded body weight, liver weight, and epididymis fat mass, blood biochemical markers, metabolites changes in liver, and gene expression involved in lipid and glucose homeostasis. The results showed that perinatal exposure to DBDPE increased the risk of obesity in mouse offspring and affected triglyceride synthesis, bile secretion, purine synthesis, mitochondrial function and glucose metabolism, furthermore, the use of HFD feeding may further exacerbate these effects. All of these results show that early-life exposure to low doses of DBDPE can promote the development of metabolic dysfunction, which in turn induces obesity.

Obesity and exposure to particular matter (PM) have become two leading global threats to public health. However, the exact mechanisms and tissue-specificity of their health effects are largely unknown. Here we investigate whether a metabolic challenge (early nutritional obesity) synergistically interacts with an environmental challenge (PM exposure) to alter genes representing key response pathways, in a tissue-specific manner. Mice subjected to 7 weeks obesogenic nutrition were exposed every other day during the final week and a half to aqueous extracts of PM collected in the city of London (UK). The expression of 61 selected genes representing key response pathways were investigated in lung, liver, white and brown adipose tissues. Principal component analysis (PCA) revealed distinct patterns of expression changes between the 4 tissues, particularly in the lungs and the liver. Surprisingly, the lung responded to the nutrition challenge. The response of these organs to the PM challenge displayed opposite patterns for some key genes, in particular, those related to the Nrf2 pathway. While the contribution to the variance in gene expression changes in mice exposed to the combined challenge were largely similar among the tissues in PCA1, PCA2 exhibited predominant contribution of inflammatory and oxidative stress responses to the variance in the lungs, and a greater contribution of autophagy genes and MAP kinases in adipose tissues. Possible involvement of alterations in DNA methylation was demonstrated by cell-type-specific responses to a methylation inhibitor. Correspondingly, the DNA methyltransferase Dnmt3a2 increased in the lungs but decreased in the liver, demonstrating potential tissue-differential synergism between nutritional and PM exposure. The results suggest that urban PM, containing dissolved metals, interacts with obesogenic nutrition to regulate diverse response pathways including inflammation and oxidative stress, in a tissue-specific manner. Tissue-differential effects on DNA methylation may underlie tissue-specific responses to key stress-response genes such as catalase and Nrf2.

Exposure of Bisphenol A (BPA) is closely associated with an increased prevalence of obesity-related metabolic syndrome. However, the potential mechanism of BPA-induced adipogenesis remains to be fully elucidated. Herein, potential mechanisms of BPA-induced adipogenesis in 3T3-L1 preadipocytes were evaluated using RNA-Seq. Then, using an early-life BPA exposure model, we further evaluated the effects of BPA exposure on lipid and glucose homeostasis. The results showed that lipid content in 3T3-L1 adipocytes was significantly increased after BPA exposure (p < 0.01) and male C57BL/6 mice with the dose of 500 μg/kg/day BPA by once-a-day oral administration for 8 weeks displayed a NAFLD-like phenotype. RNA-Seq analysis of preadipocytes showed that BPA exposure affected multiple biological processes including glycosphingolipid biosynthesis, regulation of lipolysis in adipocytes, PPAR signaling pathway and fatty acid metabolism. The dysregulation in a series of genes of mice was associated to de novo lipogenesis and lipid transport, which was linked to obesity. Importantly, we also found a significant expression increase of stearoyl-CoA desaturase 1 (SCD1) and a significant decrease of apolipoprotein D (APOD) in both fat (p < 0.01) and livers (p < 0.01) of male mice. Besides, the dysregulation of pro-inflammatory genes (TNF-α,IL-6 and SAA3) showed that BPA exposure promoted progression of hepatic inflammation. In conclusion, this study elucidated a novel mechanism in which obesity associated with BPA exposure by targeting SCD1. Exposure to BPA should be carefully examined in the chronic liver metabolic diseases.

An increasing body of evidence has linked greenspace and various health outcomes in children and adolescents, but the conclusions were inconsistent. For this review, we comprehensively summarized the measurement methods of greenspace, resultant health outcomes, and potential mechanisms from epidemiological studies in children and adolescents (aged ≤19 years). We searched for studies published and indexed in MEDLINE and EMBASE (via Ovid) up to April 11, 2022. There were a total of 9,291 studies identified with 140 articles from 28 countries finally assessed and included in this systematic review. Over 70% of the studies were conducted in highly urbanised countries/regions, but very limited research has been done in low-and middle-income countries and none in Africa. Measures of greenspace varied. Various health outcomes were reported, including protective effects of greenspace exposure on aspects of obesity/overweight, myopia, lung health, circulatory health, cognitive function, and general health in children and adolescents. The associations between greenspace exposure and other health outcomes were inconsistent, especially for respiratory health studies. We pooled odds ratios (OR) using random-effects meta-analysis for health outcomes of asthma (OR = 0.94, 95%CI: 0.84 to 1.06), allergic rhinitis (OR = 0.95; 95% CI: 0.73 to 1.25), and obesity/overweight (OR = 0.91, 95%CI: 0.84 to 0.98) with per 0.1 unit increase in normalized difference in vegetation index (NDVI). These associations have important implications for the assessment and management of urban environment and health in children and adolescents.