title: 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).
  
  
  OBJECTIVE
  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.
authors.affiliation: INSERM UMR-S 747, Université Paris Descartes, Centre Universitaire des Saints-Pères, Paris, France.
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Kim
authors.forename: Véronique
authors.initials: V
authors.lastname: Pelloux
authors.forename: Erwan
authors.initials: E
authors.lastname: Guyot
authors.forename: Joan
authors.initials: J
authors.lastname: Tordjman
authors.forename: Linh-Chi
authors.initials: LC
authors.lastname: Bui
authors.forename: Aline
authors.initials: A
authors.lastname: Chevallier
authors.forename: Claude
authors.initials: C
authors.lastname: Forest
authors.forename: Chantal
authors.initials: C
authors.lastname: Benelli
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.forename: Robert
authors.initials: R
authors.lastname: Barouki
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects; D009765:Obesity / Q000139:chemically induced* / Q000473:pathology; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001571:Benzoflavones; D016207:Cytokines; D018836:Inflammation Mediators; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; C011512:alpha-naphthoflavone; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl