The Role of Airborne PCBs in Adipogenesis, Adipose Function, and Metabolic Syndrome

University Of Iowa, Iowa City IA

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Abstract

PROJECT SUMMARY: PROJECT 2 – IMMUNOMETABOLIC EFFECTS OF PCBs ON ADIPOSE Inhalation represents a main route of exposure to PCBs, particularly for children in schools and near waterways that are contaminated with PCBs. Congeners that the ISRP has found to be at high levels in school air accumulate in adipose tissue. Published and preliminary studies demonstrate that PCB mixtures and individual congeners are cytotoxic and/or disrupt the function of adipocyte lineage cells and macrophages. Epidemiologic and rodent studies provide evidence that exposure to PCBs is associated with the development of metabolic syndrome, including disruption of glucose homeostatis, steatosis, and obesity. Western diet is also clearly a cause of metabolic syndrome but it is unknown how PCB exposures at an early age synergize with diet to disease. We hypothesize that exposure to PCBs found in school air impairs adipose lineage and adipose immune cells, disrupting adipose function and exacerbating the effects of Western Diet to contribute to metabolic syndrome. A preliminary in vivo inhalation study indicates that a 4-week early age exposure to PCB52, a congener that is at high levels in school air, causes sex-specific changes in inflammatory and oxidative stress pathways in adipose tissue. In aim 1, we propose to utilize unique inhalation technology to expose mice at an early age to a school air PCB mixture, similar to what school children would be exposed to on a regular basis, and determine how this synergizes with sex and Western Diet to cause early onset or exacerbation of symptoms of metabolic syndrome. In aim 2, we will determine how exposure to PCBs (mixtures, congeners, and metabolites) found in school air and the air of dredging sites disrupts adipose function through effects on primary human adipocyte lineage cells and macrophages. Subaim 2.1 we will utilize novel co-culture strategies that model adipose tissue to assess how PCBs affects these cells individually and crosstalk between these cells. Subaim 2.2 will determine the mechanisms by which airborne PCBs cause dysfunction of adipocyte lineage and immune cells, focusing on proinflammatory and oxidative stress pathways. In both aims we will share techniques and resources with ISRP Project 1, which is studying neurotoxic effects of PCBs. What PCB mixtures, congeners, and metabolites we use will be guided by ISRP Projects 3 and 4, that are assessing PCBs in school air and dredging sites. Our work will rely on ISRP cores for synthesis and analytical assessment of PCBs in samples. We will work with the community engagement and administrative and research translation cores to disseminate information on how PCBs affect metabolic syndrome and in research translation. The training and data management cores will provide training in advanced analytical methods, data science and data management. Our project is relevant to SRP mandates in that it will result in innovative technology to assess how PCBs affect adipose. Findings will be important for assessment of risk associated with airborne PCB exposure which will be of interest to regulatory agencies and communities subjected to PCB exposure, particularly early life exposure of children and young adults.