Pathway Genes belong to Major Targets of Persistent Organic Pollutants in Adipose Cells.
Kim MJ, Pelloux V, Guyot E, Tordjman J, Bui L-C, Chevallier A, et al. 2012. Inflammatory Environ Health Perspect :-. http://dx.doi.org/10.1289/ehp.1104282
Background: Epidemiological studies emphasized the possible role of persistent organic pollutants (POPs) in obesity and the metabolic syndrome. These pollutants are stored in adipose tissue (AT).
Objectives: To study the effects of POPs on human adipose cells and rodent AT.
Methods: Using the human Multipotent Adipose-Derived Stem (hMADS) cells, we carried out large scale gene expression analysis to identify the major pathways modified by TCDD, PCB126 and PCB153 and to evaluate their toxic effects. The effect of TCDD on gene expression and AT histology was 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 pathway. 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 by combinations of pollutants, the effects of the AhR ligands, TCDD and PCB126, were dominant when compared to those of the non dioxin-like PCB153. The effects of AhR ligands were reduced by the AhR antagonist alpha-naphtoflavone. The regulation of inflammatory pathway was observed in wild type AT but not in AhR knock-out mice.
Conclusions: Both in vitro and in vivo studies showed that adipose cells were targets of AhR ligands and suggested that inflammation was one of the main regulated pathways. These observations suggest a possible contribution of pollutants to the low-grade AT inflammation which accompanies the pathogenesis of metabolic diseases.
