Article

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: 4.39). 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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    • "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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    Environmental Research 02/2015; 138:202-216. DOI:10.1016/j.envres.2014.12.031 · 3.95 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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    • "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). "
    [Show abstract] [Hide abstract]
    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 3 T3-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.
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