Ozone Induces Systemic Metabolic Derangement Through Neuronal Stress Mechanisms Public Deposited

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  • March 20, 2019
  • Miller, Desinia
    • Affiliation: School of Medicine, Curriculum in Toxicology
  • Diabetes is reported to be the seventh leading cause of death in the United States with 90% of the cases characterized as type II diabetes. The conventional risk factors associated with diabetes are genetics, sedentary lifestyle, and high fat/high caloric diet. However, recently air pollution, such as ground level ozone, has also been postulated to contribute to diabetes, but there is limited scientific evidence. Ground level ozone is produced through the interaction of volatile organic compounds, nitric oxides and ultraviolet radiation. Ozone is known to cause pulmonary injury/inflammation but its link to peripheral metabolic effects have not been characterized. Through inhalation studies involving humans and rodent models, we examined if and how ozone exposure may change metabolism and contribute to insulin resistance, which can lead to type II diabetes. In our rodent studies, we observed that ozone exposure increases blood glucose, inhibits insulin secretion and widely affects glucose, protein and lipid metabolism. Our clinical ozone exposure study shows that humans present similar effects to rodents, especially in lipid metabolism. These types of changes over time have been linked to insulin resistance. Through surgical intervention, we also demonstrate that adrenal-derived stress hormones are essential for these ozone-induced metabolic and pulmonary effects. Further, our data indicates that these acute ozone-induced pulmonary, stress and metabolic effects persist during weekly episodic exposure subchronic exposure, but is reversible if the exposure discontinues for one week. No insulin resistance is observed in liver or muscle after subchronic ozone exposure while a decrease in β-cell insulin secretion. Overall, these data provide insight into the mechanism of how ozone may impair systemic metabolic homeostasis through a hormonal stress response without producing peripheral insulin resistance after subchronic exposure.
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Rights statement
  • In Copyright
  • Maeda, Nobuyo
  • Styblo, Miroslav
  • Kodavanti, Urmila
  • Coleman, Rosalind
  • Ghio, Andrew
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2016

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