Inflammatory Pathway Genes Belong to Major Targets of Persistent Organic Pollutants in Adipose Cells

Abstract

Background: Epidemiological studies emphasize the possible role of persistent organic pollutants (POPs) in obesity and the metabolic syndrome. These pollutants are stored in adipose tissue (AT).Objectives: Our aim was to study the effects of POPs on human adipose cells and rodent AT.Methods: Using human multipotent adipose-derived stem cells, we carried out large-scale gene expression analysis to identify the major pathways modified by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyl (PCB) congener 126 (PCB-126), and PCB-153 and to evaluate their toxic effects. The effects of TCDD on gene expression and AT histology were also assessed in mice.Results: The most significantly regulated genes in both precursor cells and adipocytes were those involved in the inflammatory/immune response, cancer, and metabolism pathways. Interestingly, the fold induction and the number of modulated genes were higher in precursors than in adipocytes, suggesting that the former could be more sensitive to the effect of pollutants. When cells were treated with combinations of pollutants, the effects of the AhR ligands TCDD and PCB-126 were dominant compared with those of the non-dioxin-like PCB-153. The effects of AhR ligands were reduced by the AhR antagonist α-naphthoflavone. The regulation of inflammatory pathway was observed in wild-type AT but not in AhR-knockout mice.Conclusions: Both in vitro and in vivo studies showed that adipose cells were targets of AhR ligands and suggest that inflammation is one of the main regulated pathways. These observations suggest a possible contribution of pollutants to low-grade AT inflammation that accompanies the pathogenesis of metabolic diseases.

Persistent organic pollutants distribution in lipoprotein fractions in relation to cardiovascular disease and cancer

“…On the other hand, an in vitro study has suggested that LDL-receptors play a minor role in the cellular uptake of DDTlipoprotein complexes (Hjelmborg et al 2008). Since POPs have been described to be carcinogenic (National Toxicology Program 2006), affecting gene expression (Mitra et al 2012), be pro-inflammatory (Kim et al 2012) and to cause oxidative stress (Abdollahi et al 2004), they may, once inside the cells, contribute to the initiation of tumors as well as tumor progression. It is also possible that POPs may alter LDL function through effects on apolipoproteins (Arehart et al 2004).…”

Conceptual heuristic models of the interrelationships between obesity and the occupational environment

“…It is also associated with various health problems including musculoskeletal disorders (MSD), asthma, liver disease, and cardiovascular disease (CVD) (7)(8)(9)(10). Moreover, neurohormonal and endocrine pathway disruption has been associated with obesity (11,12). Work factors, including sedentary work and taskrelated biomechanics, have been reported as risks for obesity (13)(14)(15).…”

Evaluation of Relationship Between Obesity and Endocrine Disrupting Chemicals-II: Polychlorinated Biphenyls: Review

“…PCB'lerin birikme eğilimleri yüzünden insanlar su kaynaklarında bulunan miktarın çok daha yüksek miktarlarına maruz kalmaktadır. 27,28,[31][32][33][34] POLİKLORLU BİFENİLLER VE DOZ KAVRAMI Düşük doz PCB maruziyetinin vücut ağırlığı ile doğru orantılı olduğu; yüksek doz PCB temasının ise ters orantılı olduğu bildirilmiştir. Bu kimyasal maddelerin obezite üzerine etkileri doz, maruziyet dönemi, cinsiyet ve kimyasal yapısına bağlı olarak değişiklik göstermektedir.…”

“…Bu kimyasal maddelerin obezite üzerine etkileri doz, maruziyet dönemi, cinsiyet ve kimyasal yapısına bağlı olarak değişiklik göstermektedir. 34 Yapılan son çalışmalarla, az klorlanmış PCB'lerin obeziteyle çok fazla ilişkilendirilmediği ve doz-yanıt eğrilerinin ters U şeklinde olduğu belirlenmiştir. Diğer taraftan, çok klorlanmış PCB'lerle obezite arasında ters ve daha anlamlı bir ilişki olduğu bulunmuştur.…”