Diabetes, Metabolic Syndrome, and Obesity in Relation to Serum Dioxin Concentrations: The Seveso Women’s Health Study

Warner, Marcella; Mocarelli, Paolo; Brambilla, Paolo; Wesselink, Amelia K.; Samuels, Steven J.; Signorini, Stefano; Eskenazi, Brenda

doi:10.1289/ehp.1206113

Cited by 86 publications

(76 citation statements)

References 51 publications

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“…The NHANES 1999–2002 study showed an association between waist circumferences and BMI in subjects with detectable levels of POPs, making the chemicals plausible contributors to the obesity epidemic [92]. This also hold true for the adults, where a clear evidence for associations with the highly chlorinated PCBs and OC pesticide with existence or development of obesity [51, 79, 102, 103]. …”

Section: Endocrine Disrupting Chemicals (Pcbs Exposures) and Developmmentioning

confidence: 99%

Biomarkers Linking PCB Exposure and Obesity.

Ghosh¹,

Murínová²,

Trnovec³

et al. 2014

CPB

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Recently the prevalence of obesity has increased dramatically across much of the world. Obesity, as a complex, multifactorial disease, and its health consequences probably result from the interplay of environmental, genetic, and behavioral factors. Several lines of evidence support the theory that obesity is programmed during early development and that environmental exposures can play a key role. We therefore hypothesize that the current epidemic might associated with the influence of chemical exposures upon genetically controlled developmental pathways, leading to metabolic disorders. Some environmental chemicals, such as PCBs and pesticide residues, are widespread in food, drinking water, soil, and they exert multiple effects including estrogenic on cellular processes; some have been shown to affect the development of obesity, insulin resistance, type 2 diabetes, and metabolic syndrome. To bring these lines of evidence together and address an important health problem, this narrative review has been primarily designed to address PCBs exposures that have linked with human disease, obesity in particular, and to assess the effects of PCBs on gene expression in a highly-exposed population. The results strongly suggest that further research into the specific mechanisms of PCBs-associated diseases is warranted.

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Section: Endocrine Disrupting Chemicals (Pcbs Exposures) and Developmmentioning

confidence: 99%

Biomarkers Linking PCB Exposure and Obesity.

Ghosh¹,

Murínová²,

Trnovec³

et al. 2014

CPB

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“…TCDD exposures are linked to several complex disease states in human cohorts including diabetes, metabolic syndrome, and cancer (Leng et al, 2014;Marinkovic et al, 2010;Uemura et al, 2009;Warner et al, 2013). TCDD is a potent activator of the aryl hydrocarbon receptor (AHR), an environment-sensing protein within the PAS superfamily (McIntosh et al, 2010).…”

mentioning

confidence: 99%

The Influence of Human Interindividual Variability on the Low-Dose Region of Dose-Response Curve Induced by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Primary B Cells

Dornbos¹,

Crawford²,

Kaminski³

et al. 2016

Toxicol. Sci.

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The influence of interindividual variability is not typically assessed in traditional toxicological studies. Given that chemical exposures occur in heterogeneous populations, this knowledge gap has the potential to cause undue harm within the realms of public health and industrial and municipal finances. A recent report from the National Research Council (NRC) suggests that when accounting for interindividual variation in responses, traditionally assumed nonlinear dose-response relationships (DRRs) for noncancer-causing endpoints would better be explained with a linear relationship within the lowdose region. To address this knowledge gap and directly test the NRC's assumption, this study focused on assessing the DRR between 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) exposure and immune suppression in a cohort of unique human donors. Human B cells were isolated from 51 individual donors and treated with logarithmically increasing concentrations of TCDD (0-30 nM TCDD). Two endpoints sensitive to TCDD were assessed: (1) number of IgM-secreting B cells and (2) quantity of IgM secreted. The results show that TCDD significantly suppressed both the number of IgM-secreting B cells and the quantity of IgM secreted (P < .05). Statistical model comparisons indicate that the low-dose region of the two DRRs is best explained with a nonlinear relationship. Rather than assuming low-dose linearity for all noncancer-causing DRRs, our study suggests the need to consider the specific mode of action of toxicants and pharmaceuticals during risk-management decision making.Key words: TCDD; AHR; human B cells; dose response; risk assessment; genetic variability.Understanding of the dose-response relationship (DRR) for any given chemical lies at the heart of risk assessment. Traditionally, data derived from lab-based toxicology studies are extrapolated in assessing the potential adverse health effects of chemicals in the human population. As traditional laboratory-based toxicology studies are performed on a small number of individuals or inbred mouse strains and as chemical exposures occur in a heterogeneous population of individuals, there lies a disconnect between lab-based toxicology and population-level risk assessment. Little is known regarding the degree of variability in a DRR within a heterogeneous population (Rhomberg, 2011).A recent report published by the National Research Council (NRC) suggested that interindividual variability within the human population would effectively linearize the low-dose region of DRRs for all noncancer-causing chemicals (NRC, 2009).

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“…Acute TCDD exposure induces a wasting syndrome characterized by weight loss, adipose derangements, hyperlipidemia, ectopic lipid deposition, and hypoinsulinemia [79]. Conversely, multiple epidemiologic studies link TCDD to diabetes and hyper insulinemia [80,81]. In β-cell models, TCDD effects are similarly conflicting.…”

Section: Context-dependent MDC Actionmentioning

confidence: 99%

Polluted Pathways: Mechanisms of Metabolic Disruption by Endocrine Disrupting Chemicals

Mimoto

Nadal

Sargis

2017

Curr Envir Health Rpt

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Purpose of review Environmental toxicants are increasingly implicated in the global decline in metabolic health. Focusing on diabetes, herein the molecular and cellular mechanisms by which metabolism disrupting chemicals (MDCs) impair energy homeostasis are discussed. Recent findings Emerging data implicate MDC perturbations in a variety of pathways as contributors to metabolic disease pathogenesis, with effects in diverse tissues regulating fuel utilization. Potentiation of traditional metabolic risk factors, such as caloric excess, and emerging threats to metabolism, such as disruptions in circadian rhythms, are important areas of current and future MDC research. Increasing evidence also implicates deleterious effects of MDCs on metabolic programming that occur during vulnerable developmental windows, such as in utero and early post-natal life as well as pregnancy. Summary Recent insights into the mechanisms by which MDCs alter energy homeostasis will advance the field’s ability to predict interactions with classical metabolic disease risk factors and empower studies utilizing targeted therapeutics to treat MDC-mediated diabetes.

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Diabetes, Metabolic Syndrome, and Obesity in Relation to Serum Dioxin Concentrations: The Seveso Women’s Health Study

Cited by 86 publications

References 51 publications

Biomarkers Linking PCB Exposure and Obesity.

Biomarkers Linking PCB Exposure and Obesity.

The Influence of Human Interindividual Variability on the Low-Dose Region of Dose-Response Curve Induced by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Primary B Cells

Polluted Pathways: Mechanisms of Metabolic Disruption by Endocrine Disrupting Chemicals

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