Adipokines, cytokines secreted by adipose tissue, may contribute to obesity-related metabolic disease. The role of environmental phenols and parabens in racial difference in metabolic disease burden has been suggested, but there is limited evidence. We examined the cross-sectional associations of urinary phenols and parabens with adipokines and effect modification by race. Urinary concentrations of 6 phenols (bisphenol-A, bisphenol-F, 2,4-diclorophenol, 2,5-diclorophenol, triclosan, benzophenone-3) and 4 parabens (methyl-paraben, ethyl-paraben, propyl-paraben, butyl-paraben) were measured in 2002–2003 among 1200 women (mean age = 52.6) enrolled in the Study of Women's Health Across the Nation Multi-Pollutant Study. Serum adipokines included adiponectin, high molecular weight (HMW)-adiponectin, leptin, soluble leptin receptor (sOB-R). Linear regression models were used to estimate the adjusted percentage change in adipokines per inter-quantile range (IQR) increase in standardized and log-transformed levels of individual urinary phenols and parabens. Bayesian kernel machine regression (BKMR) was used to evaluate the joint effect of urinary phenols and parabens as mixtures. Participants included white (52.5%), black (19.3%), and Asian (28.1%) women. Urinary 2,4-dichlorophenol was associated with 6.02% (95% CI: 1.20%, 10.83%) higher HMW-adiponectin and urinary bisphenol-F was associated with 2.60% (0.48%, 4.71%) higher sOB-R. Urinary methyl-paraben was associated with lower leptin in all women but this association differed by race: 8.58% (−13.99%, −3.18%) lower leptin in white women but 11.68% (3.52%, 19.84%) higher leptin in black women (P interaction = 0.001). No significant associations were observed in Asian women. Additionally, we observed a significant positive overall effect of urinary phenols and parabens mixtures in relation to leptin levels in black, but not in white or Asian women. Urinary bisphenol-F, 2,4-dichlorophenol and methyl-paraben may be associated with favorable profiles of adipokines, but methyl-paraben, widely used in hair and personal care products, was associated with unfavorable leptin levels in black women. Future studies are needed to confirm this racial difference.

The present paper reports on the interrelationships of fish, parasites and the bioaccumulation of hazardous organic compounds in the Zemplínska Šírava water reservoir in eastern Slovakia, which is heavily polluted with polychlorinated biphenyls (PCBs). The concentrations of these contaminants were measured in various fish matrices (dorsal and abdominal muscle tissues, hepatopancreas, intestine wall and adipose tissue) of the freshwater bream, Abramis brama (Cyprinidae), and in its intestinal parasite Caryophyllaeus laticeps (Cestoda), which was used for the first time as a model for a PCB bioaccumulation study. Regarding the fish, the highest concentrations of PCBs were found in the intestine, followed by hepatopancreas and muscle tissues. The amounts of PCBs were higher in abdominal muscles than in their dorsal parts. Concentrations of ∑PCBs above the limits set by European regulations were detected in both muscle parts in the fish, confirming the persistent unfavorable conditions in this locality and high risk for biota and humans. Based on bioconcentration factor values (BCFs), PCBs reached much higher levels in cestodes compared to bream matrices. Some significant differences in PCB amounts between infected and uninfected bream were determined. Fulton's condition factor (CF) significantly differed in infected and non-infected fish (p ˂ 0.05), with CF values surprisingly lower in fish free of parasites compared to parasitized fish, which suggests a “mutualistic” relationship between the parasite and its host.

Endometriosis is a gynaecological disease characterised by the presence of endometriotic tissue outside of the uterus impacting a significant fraction of women of childbearing age. Evidence from epidemiological studies suggests a relationship between risk of endometriosis and exposure to some organochlorine persistent organic pollutants (POPs). However, these chemicals are numerous and occur in complex and highly correlated mixtures, and to date, most studies have not accounted for this simultaneous exposure. Linear and logistic regression models are constrained to adjusting for multiple exposures when variables are highly intercorrelated, resulting in unstable coefficients and arbitrary findings. Advanced machine learning models, of emerging use in epidemiology, today appear as a promising option to address these limitations. In this study, different machine learning techniques were compared on a dataset from a case-control study conducted in France to explore associations between mixtures of POPs and deep endometriosis. The battery of models encompassed regularised logistic regression, artificial neural network, support vector machine, adaptive boosting, and partial least-squares discriminant analysis with some additional sparsity constraints. These techniques were applied to identify the biomarkers of internal exposure in adipose tissue most associated with endometriosis and to compare model classification performance. The five tested models revealed a consistent selection of most associated POPs with deep endometriosis, including octachlorodibenzofuran, cis-heptachlor epoxide, polychlorinated biphenyl 77 or trans-nonachlor, among others. The high classification performance of all five models confirmed that machine learning may be a promising complementary approach in modelling highly correlated exposure biomarkers and their associations with health outcomes. Regularised logistic regression provided a good compromise between the interpretability of traditional statistical approaches and the classification capacity of machine learning approaches. Applying a battery of complementary algorithms may be a strategic approach to decipher complex exposome-health associations when the underlying structure is unknown.

In the general population, chronic exposure to low-dose persistent organic pollutants (POPs), particularly organochlorine pesticides (OCPs), has been recently linked to many chronic diseases. Widespread contamination of the food chain and human adipose tissue has made avoiding exposure to these chemicals impossible; thus, alternative strategies for decreasing the chemical burden must be investigated. Recently, macronutrient intake was found to significantly modify the toxicokinetics of POPs in animal experimental studies. Thus, we evaluated whether macronutrient intake was related to serum concentrations of OCPs in healthy adults without cardio-metabolic diseases. Subjects included 1,764 adults, aged 20 years or above, who participated in the National Health and Nutrition Examination Survey 1999–2004. Macronutrient intake was assessed based on a 24-h dietary recall interview. Six individual OCPs commonly detected among the general population were evaluated as markers of OCPs and other coexisting lipophilic chemicals stored in adipose tissue and released into circulation. High fat intake was associated with lower concentrations of OCPs, while high carbohydrate intake showed the opposite result. When three types of fats were individually evaluated, both saturated fatty acids and monounsaturated fatty acids, but not polyunsaturated fatty acids, were inversely associated with serum concentrations of OCPs. Adjustment for possible confounders did not change the results. When stratified by age, gender, body mass index, and physical activity, these associations were similar in most subgroups. Thus, similar to the findings observed in animal experimental studies, a moderate-fat diet with low carbohydrate intake was related to low serum concentrations of OCPs in humans. Although these findings need to be replicated, changing dietary macronutrient intake can be investigated as a practical strategy for dealing with unavoidable lipophilic chemical mixtures such as OCPs in modern society.

Blubber samples of Indo-Pacific bottlenose (Tursiops aduncus) and spinner (Stenella longirostris) dolphins from Zanzibar, East Africa, were analyzed for a wide range of organohalogen compounds. Methoxylated polybrominated diphenyl ethers (MeO-BDEs), presumably biogenic, were found at higher concentrations than anthropogenic organochlorine pesticides (OCPs). Only traces of industrial pollutants, such as polychlorinated biphenyls, were detected. The OCP levels found off Zanzibar were lower than those reported from other regions while MeO-BDE levels were higher. The relative composition of the OCPs indicated recent use of lindane (γ-hexachlorocyclohexane) and aged residues of DDT and technical HCH. Placental transfer was estimated to 2.5% and 0.5% of the total burden of OCPs and MeO-BDEs, respectively. Overall transfer from mother to calf in Indo-Pacific bottlenose dolphins was estimated to 72% and 85% for the OCPs and MeO-BDEs burdens, respectively. Health effects of MeO-BDEs are not known, but structural similarities with well-known environmental toxins are cause for concern.

In the frame of a French monitoring program, tri- to deca- polybromodiphenylethers (PBDE) have been measured in maternal and cord serum, adipose tissue, and breast milk samples, collected from 93 volunteer women during caesarean deliveries. The seven major tri- to heptaBDE (BDE-28, 47, 99, 100, 153, 154, and 183) were detected in adipose tissue and breast milk with cumulated median values of 2.59 and 2.51 ng g-1 l w. Nine highly brominated octa- to decaBDE (BDE-196, 197, 201, 202, 203, 206, 207, 208 and 209) was performed in the same samples, with cumulated median values of 2.73 and 3.39 ng g-1 l w in adipose tissue and breast milk, respectively. At this opposite, median levels of octa- to decaBDE in maternal and cord serum appeared significantly higher than the levels of tri- to heptaBDE in the same matrices, i.e. 8.85 and 12.34 versus 0.98 and 0.69 ng g-1 l w, respectively. This study provides the first data at the French level regarding the occurrence of PBDE in human, and demonstrates the exposure of both human foetus at late stage of pregnancy and newborn at early stages of life through breastfeeding with special emphasis on the presence of highly brominated compounds.

Brominated flame retardants (BFRs) are chemicals employed to lower the flammability of several objects. These endocrine disruptor chemicals are lipophilic and persistent in the environment. Due to these characteristics some have been restricted or banned by the European Union, and replaced by several new chemicals, the novel BFRs (NBFRs). BFRs are widely detected in human samples, such as adipose tissue and some were linked with altered thyroid hormone levels, liver toxicity, diabetes and metabolic syndrome in humans. However, the disturbance in lipid metabolism caused by BFRs with emphases to NBFRs remains poorly understood. In this study, we used a pre-adipocyte (3T3-L1) cell line and a hepatocyte (HepG2) cell line to investigate the possible lipid metabolism disruption caused by four BFRs: hexabromobenzene (HBB), pentabromotoluene (PBT), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB) and hexabromocyclododecane (HBCD). For that purpose, proliferation and Oil Red O assays, as well as, medium fatty acids profile evaluation using Gas chromatography and RNA extraction for quantitative RT-PCR assays were performed. We detected a significant reduction in the proliferation of preadipocytes and an increased lipid accumulation during differentiation caused by HBB. This BFR also lead to a significant increased expression of IL-1β and decreased expression of PGC-1α and adiponectin. Nevertheless, PBT, TBB and HBCD show to increase lipid accumulation in hepatocytes. PBT also display a significant increase of PPARγ gene expression. Lipid accumulation in the cells can occur by diverse mechanisms depending on the BFR. These results highlight the importance of endocrine disruptor compounds in obesity etiopathogeny.

Bisphenol S is an endocrine disruptor exhibiting metabolic disturbances, especially following perinatal exposures. To date, no data are available on the obesogen effects of BPS in a mutligenerational issue.We investigated obesogen effects of BPS in a multigenerational study by focusing on body weight, adipose tissue and plasma parameters in male and female mice.Pregnant C57BL6/J mice were exposed to BPS (1.5 μg/kg bw/day ie a human equivalent dose of 0.12 μg/kg bw/day) by drinking water from gestational day 0 to post natal day 21. All offsprings were fed with a high fat diet during 15 weeks. Body weight was monitored weekly and fat mass was measured before euthanasia. At euthanasia, blood glucose, insuline, triglyceride, cholesterol and no esterified fatty acid plasma levels were determined and gene expressions in visceral adipose tissue were assessed. F1 males and females were mated to obtain the F2 generation. Likewise, the F2 mice were cross-bred to obtain F3. The same analyses were performed.In F1 BPS induced an overweight in male mice associated to lipolysis gene expressions upregulation. In F1 females, dyslipidemia was observed. In F2, BPS exposure was associated to an increase in body weight, fat and VAT masses in males and females. Several plasma parameters were increased but with a sex related pattern (blood glucose, triglycerides and cholesterol in males and NEFA in females). We observed a down-regulation in mRNA expression of gene involved in lipogenesis and in lipolysis for females but only in the lipogenesis for males. In F3, a decrease in VAT mass and an upregulation of lipogenesis gene expression occurred only in females.BPS perinatal exposure induced sex-dependent obesogen multigenerational effects, the F2 generation being the most impacted. Transgenerational disturbances persisted only in females.

In this study, levels of dechlorane plus (DP) in breast milk and matched adipose tissue samples were measured from 54 women living in Wenling, China. Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) were measured simultaneously for comparison. The levels of ∑DPs/∑PBDEs varied from less than one to several dozens of ng g⁻¹ lipid weight (lw) in matrices and the levels of ∑PCBs varied between several to hundreds of ng g⁻¹ lw. In the same matrix, ∑DPs and ∑PCBs/∑PBDEs showed a significant relationship (p < 0.05), indicating that they shared common sources. Accordingly, there was a strong association of lipid-adjusted concentrations of individual compounds (BDE-209 excluded) between matrices (p < 0.001), suggesting that breast milk could be a proxy for adipose tissue in human bioburden monitoring of these compounds. The predicted lipid-adjusted milk/adipose ratios varied from 0.62 to 1.5 but showed significant differences (p<0.001) between compounds, suggesting a compound-specific transfer between milk lipids and adipose tissue lipids. Specifically, the milk/adipose ratios for syn-DP and anti-DP (−1.40 and 1.3, respectively) were significantly higher than those of CB congeners and hexa/hepta-BDE congeners (p < 0.05). In addition, unlike PCBs/PBDEs (excluding BDE-209), DP’s hydrophobicity might not be responsible for its preferable distribution in milk lipids. Instead, the interaction with nonlipid factors played a key role. The fraction of anti-DP between the two kinds of matrices was not significantly different, suggesting that the biochemical transfer processes may not be efficient enough to distinguish DP isomers. Nevertheless, the congener patterns of PCBs/PBDEs gave a clue about the compound-specific transfer between milk and adipose tissue. To our knowledge, this is the first to report the relationships of DP between adipose tissue and breast milk. These results could provide useful and in-depth information on biomonitoring of DP and facilitate the understanding of the accumulation and excretion potentials of DP and its distribution-related mechanism in humans.

There is increasing evidence linking levels of trace elements (TEs) in adipose tissue with certain chronic conditions (e.g., diabetes or obesity). The objectives of this study were to assess concentrations of a selection of nine essential and possibly-essential TEs in adipose tissue samples from an adult cohort and to explore their socio-demographic, dietary, and lifestyle determinants. Adipose tissue samples were intraoperatively collected from 226 volunteers recruited in two public hospitals from Granada province. Trace elements (Co, Cr, Cu, Fe, Mn, Mo, Se, V, and Zn) were analyzed in adipose tissue by high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). Data were collected on socio-demographic characteristics, lifestyle, diet, and health status by face-to-face interview. Predictors of TE concentrations were assessed by using multivariable linear and logistic regression. All TEs were detected in all samples with the exception of Se (53.50%). Iron, zinc, and copper showed the highest concentrations (42.60 mg/kg, 9.80 mg/kg, and 0.68 mg/kg, respectively). Diet was the main predictor of Cr, Fe, Mo, and Se concentrations. Body mass index was negatively associated with all TEs (β coefficients = −0.018 to −0.593, p = 0.001–0.090) except for Mn and V. Age showed a borderline-significant positive correlation with Cu (β = 0.004, p = 0.089). Residence in a rural or semi-rural area was associated with increased Co, Cr, Fe, Mo, Mn, V and Zn concentrations and with β coefficients ranging from 0.196 to 0.544 (p < 0.05). Furthermore, individuals with higher educational level showed increased Cr, Co, Fe and V concentrations (β coefficients = 0.276–0.368, p = 0.022–0.071). This is the first report on the distribution of these TEs in adipose tissue and on their determinants in a human cohort and might serve as an initial step in the elucidation of their clinical relevance.