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

Environ Health Perspect. 2012 Apr;120(4):508-14. doi: 10.1289/ehp.1104282. Epub 2012 Jan 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipose Tissue / cytology
  • Adipose Tissue / drug effects
  • Animals
  • Benzoflavones / pharmacology
  • Body Weight / drug effects
  • Cell Differentiation*
  • Cytokines / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation Mediators / metabolism
  • Mice
  • Mice, Knockout
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / drug effects
  • Obesity / chemically induced*
  • Obesity / pathology
  • Polychlorinated Biphenyls / toxicity*
  • Polychlorinated Dibenzodioxins / toxicity*
  • Real-Time Polymerase Chain Reaction
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Weight Gain / drug effects

Substances

  • Benzoflavones
  • Cytokines
  • Inflammation Mediators
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon
  • alpha-naphthoflavone
  • Polychlorinated Biphenyls
  • 3,4,5,3',4'-pentachlorobiphenyl
  • 2,4,5,2',4',5'-hexachlorobiphenyl