A delayed proinflammatory response of human preadipocytes to PCB126 is dependent on the aryl hydrocarbon receptor
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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.
KeywordsAdipocytes Preadipocytes Fat PCB Inflammation Diabetes AhR
We thank Dr. Patrick Ten Eyck at the Institute for Clinical and Translational Science, University of Iowa, for the statistical analysis. We also thank Hans Joachim-Lehmler of the University of Iowa Superfund Synthesis Core for supplying PCB126, Anna Chaly for the technical support, and Gopi Gadupudi for the advice.
Compliance with ethical standards
This work was supported by a seed grant from the University of Iowa Center for Health Effects of Environmental Contamination (CHEEC), a pilot grant from the University of Iowa Environmental Health Sciences Research Center (grant number P30 ES05605), and a Fraternal Order of Eagles Diabetes Research Center Award given to AJK and the Iowa Superfund Research Program (grant number P42 ES 013661) awarded to LWR.
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