Obesity and Persistent Organic Pollutants: Possible Obesogenic Effect of Organochlorine Pesticides and Polychlorinated Biphenyls

Department of Endocrinology, Diabetology and Clinical Pharmacology, Antwerp University Hospital and University of Antwerp, Antwerp, Belgium.
Obesity (Impact Factor: 3.73). 04/2011; 19(4):709-14. DOI: 10.1038/oby.2010.133
Source: PubMed

ABSTRACT Persistent organic pollutants (POPs) are endocrine-disrupting chemicals associated with the development of the metabolic syndrome and type 2 diabetes. In humans, little is known about their role in the potential origin of obesity. This study aims to assess the associations between serum levels of POPs and the prevalence of obesity in a cohort of obese and lean adult men and women. POP serum samples were investigated cross-sectionally in 98 obese and 47 lean participants, aged ≥18 years. Serum samples were analyzed for the presence of polychlorinated biphenyl (PCB) congeners 153, 138, 180, and 170 and for the organochlorine pesticides, dichloro-diphenyl-dichloroethylene (pp-DDE), and β-hexachlorocyclohexane (βHCH). We established a significant negative correlation between BMI, waist, fat mass percentage, total and subcutaneous abdominal adipose tissue, and serum levels of PCB 153, 180, 170, and the sumPCBs. For βHCH, we demonstrated a positive correlation with BMI, waist, fat mass percentage, and total and subcutaneous abdominal adipose tissue. PCBs 180, 170, and the sum of PCBs correlated significantly negative with homeostasis model assessment for insulin resistance (HOMA(IR)). βHCH correlated significantly positively with HOMA(IR). A strong correlation was established between all POP serum levels and age. We established a positive relationship between high serum levels of βHCH and BMI and HOMA(IR), whereas serum PCB levels were inversely correlated with BMI and HOMA(IR). Combined, these results suggest that the diabetogenic effect of low-dose exposure to POPs might be more complicated than a simple obesogenic effect.

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Available from: Luc Frans Van Gaal, Sep 01, 2014
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    • "All rights reserved. (Longnecker and Daniels, 2001; Vasiliu et al., 2006; Carpenter, 2011; Dirinck et al., 2011; Lee et al., 2011). There is growing evidence that perturbations of central endocrine regulatory systems by the endocrine disrupting chemicals (EDCs; e.g. "
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    ABSTRACT: Our earlier gene-expression studies with a Slovak PCBs-exposed population have revealed possible disease and disorder development in accordance with epidemiological studies. The present investigation aimed to develop an in vitro model system that can provide an indication of disrupted biological pathways associated with developing future diseases, well in advance of the clinical manifestations that may take years to appear in the actual human exposure scenario. We used human Primary Blood Mononuclear Cells (PBMC) and exposed them to a mixture of human equivalence levels of PCBs (PCB-118, -138, -153, -170, -180) as found in the PCBs-exposed Slovak population. The microarray studies of global gene expression were conducted on the Affymetrix platform using Human Genome U133 Plus 2.0 Array along with Ingenuity Pathway Analysis (IPA) to associate the affected genes with their mechanistic pathways. High-throughput qRT-PCR Taqman Low Density Array (TLDA) was done to further validate the selected 6 differentially expressed genes of our interest, viz., ARNT, CYP2D6, LEPR, LRP12, RRAD, TP53, with a small population validation sample (n=71). Overall, we revealed a discreet gene expression profile in the experimental model that resembled the diseases and disorders observed in PCBs-exposed population studies. The disease pathways included endocrine system disorders, genetic disorders, metabolic diseases, developmental disorders, and cancers, strongly consistent with the evidence from epidemiological studies. These gene finger prints could lead to the identification of populations and subgroups at high risk for disease, and can pose as early disease biomarkers well ahead of time, before the actual disease becomes visible. Copyright © 2015 Elsevier Inc. All rights reserved.
    Environmental Research 02/2015; 138:202-216. DOI:10.1016/j.envres.2014.12.031 · 4.37 Impact Factor
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    • "The exposure to PCBs is associated to adverse effects on human and animal health [19], [20]. Among others, PCBs are involved in endocrine disruption, immuno- and neuro-toxicity as well as in the development of cardiovascular diseases and type-2 diabetes [21]–[25]. A correlation between the rise of persistent organic pollutants (POPs), such as PCBs, in the serum and the alterations of skeletal muscle oxidative capacity has been suggested in humans [16]. "
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    ABSTRACT: Background Polychlorinated biphenyls (PCBs) are persistent organic pollutants. Due to their lipophilic character, they are preferentially stored within the adipose tissue. During the mobilisation of lipids, PCBs might be released from adipocytes into the bloodstream. However, the mechanisms associated with the release of PCBs have been poorly studied. Several in vivo studies followed their dynamics of release but the complexity of the in vivo situation, which is characterised by a large range of pollutants, does not allow understanding precisely the behaviour of individual congeners. The present in vitro experiment studied the impact of (i) the number and position of chlorine atoms of PCBs on their release from adipocytes and (ii) the presence of other PCB congeners on the mobilisation rate of such molecules. Methodology/Principal Findings Differentiated rat adipocytes were used to compare the behaviour of PCB-28, -118 and -153. Cells were contaminated with the three congeners, alone or in cocktail, and a lipolysis was then induced with isoproterenol during 12 hours. Our data indicate that the three congeners were efficiently released from adipocytes and accumulated in the medium during the lipolysis. Interestingly, for a same level of cell lipids, PCB-153, a hexa-CB with two chlorine atoms in ortho-position, was mobilised slower than PCB-28, a tri-CB, and PCB-118, a penta-CB, which are both characterised by one chlorine atom in ortho-position. It suggests an impact of the chemical properties of pollutants on their mobilisation during periods of negative energy balance. Moreover, the mobilisation of PCB congeners, taken individually, did not seem to be influenced by the presence of other congeners within adipocytes. Conclusion/Significance These results not only highlight the obvious mobilisation of PCBs from adipocytes during lipolysis, in parallel to lipids, but also demonstrate that the structure of congeners defines their rate of release from adipocytes.
    PLoS ONE 09/2014; 9(9):e106495. DOI:10.1371/journal.pone.0106495 · 3.23 Impact Factor
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    • "Altering AT differentiation, metabolism and function, these pollutants could affect not only the physiological role of AT, but also the development of obesity-associated diseases (Casals-Casas and Desvergne, 2011; Dirinck et al., 2011; Schug et al., 2011). "
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    ABSTRACT: Non dioxin-like polychlorinated biphenyls (NDL PCBs) are highly lipophilic environmental contaminants that accumulate in lipid-rich tissues, such as adipose tissue. Here, we reported the effects induced by PCB 101, 153 and 180, three of the six NDL-PCBs defined as indicators, on mature 3T3-L1 adipocytes. We observed an increase in lipid content, in leptin gene expression and a reduction of leptin receptor expression and signalling, when cells were exposed to PCBs, alone or in combination. These modifications were consistent with the occurrence of "leptin-resistance" in adipose tissue, a typical metabolic alteration related to obesity. Therefore, we investigated how PCBs affect the expression of pivotal proteins involved in the signalling of leptin receptor. We evaluated PCBs effect on the intracellular pathway JAK/STAT, determining the phosphorylation of STAT3, a downstream activator of the transcription of leptin gene targets, and the expression of SOCS3 and PTP1B, two important regulators of leptin resistance. In particular, PCB 153 and 180 or all PCB combination induced a significant reduction in pSTAT3/STAT3 ratio and an increase in PTP1B and SOCS3, evidencing an additive effect. The impairment of leptin signalling was associated to the reduction of AMPK/ACC pathway activation, leading to the increase in lipid content. These pollutants were also able to increase the transcription of inflammatory cytokines (IL-6 and TNFα). It is worthy to note that the PCB concentrations used are comparable to levels detectable in human adipose tissue. Our data strongly support the hypothesis that NDL PCBs may interfere with the lipid metabolism contributing to the development of obesity and related diseases.
    Toxicology and Applied Pharmacology 06/2014; 279(3). DOI:10.1016/j.taap.2014.06.016 · 3.71 Impact Factor
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