A delayed proinflammatory response of human preadipocytes to PCB126 is dependent on the aryl hydrocarbon receptor

Environ Sci Pollut Res Int. 2018 Jun;25(17):16481-16492. doi: 10.1007/s11356-017-9676-z. Epub 2017 Jul 11.

Abstract

Inflammation in adipose tissue is recognized as a causative factor in the development of type II diabetes. Adipocyte hypertrophy as well as bacterial and environmental factors have been implicated in causing inflammation in mature adipocytes. Exposure to persistent organic pollutants such as polychlorinated biphenyls (PCBs) has been associated with the development of type II diabetes. We show here that PCB126, a dioxin-like PCB, activates a robust proinflammatory state in fat cell precursors (preadipocytes). The response was found to be dependent on aryl hydrocarbon receptor (AhR) activation, although induction of the response was delayed compared to upregulation of CYP1A1, a classic AhR-responsive gene. Treatment of preadipocytes with a nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) inhibitor partially attenuated the PCB126-induced inflammatory response and partly, but not completely, ameliorated disruption of adipogenesis caused by PCB126. Our results indicate a role for PCB126 in mediating an inflammatory response through AhR in preadipocytes that interferes with adipogenesis.

Keywords: Adipocytes; AhR; Diabetes; Fat; Inflammation; PCB; Preadipocytes.

MeSH terms

  • Adipocytes / chemistry*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Dioxins / chemistry*
  • Environmental Pollutants / adverse effects
  • Environmental Pollutants / chemistry
  • Humans
  • Inflammation / chemically induced
  • NF-kappa B / chemistry*
  • Polychlorinated Biphenyls / chemistry*
  • Polychlorinated Biphenyls / pharmacology
  • Polychlorinated Dibenzodioxins / chemistry*
  • Receptors, Aryl Hydrocarbon / chemistry*
  • Receptors, Aryl Hydrocarbon / metabolism

Substances

  • Dioxins
  • Environmental Pollutants
  • NF-kappa B
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon
  • Polychlorinated Biphenyls