Effects of PCBs on adipocytes and the development of metabolic syndrome

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Project Period: 
Project Investigator(s): 
A.J. Klingelhutz, Department of Microbiology, The University of Iowa

Recent epidemiological studies indicate that exposure to polychlorinated biphenyls (PCBs) is associated with an increased risk of metabolic syndrome, a group of disorders that includes obesity, glucose intolerance, high cholesterol, and hypertension. Metabolic syndrome increases the risk of developing type 2 diabetes. PCBs accumulate in adipocytes, which are known to play a key role in the genesis of metabolic syndrome. Recently generated extended lifespan human pre-adipocytes will provide a unique opportunity to assess the short and long term effects of PCBs on adipocyte biology. These cells will be used to test the hypothesis that exposure of adipocytes to PCBs causes long-term effects on gene expression to alter adipocyte differentiation and function. This study will lead to further understanding of how PCBs cause metabolic syndrome, may provide useful biomarkers for assessment of disease risk, and could point to new targets for therapy.

Project Results: 

PCBs are contaminants of water, air, and food. The researchers' findings may be important for determining how PCB exposure leads to human disease. Further, the model systems developed can aid in evaluation of how other environmental contaminants may affect obesity and the development of diabetes.

The study had four key findings.

  1. PCB126 inhibits the proper development of preadipocytes to adipocytes
  2. PCB126 acts through the aryl hydrocarbon receptor (AhR) in preadipocytes
  3. Activation of AhR in preadipocytes causes a proinflammatory response that inhibits proper adipogenesis
  4. Disruption of adipogenesis by PCB126 may be involved in the development of metabolic syndrome