Air pollution and neuroendocrine stress-mediated systemic metabolic and inflammatory response
Citation:
Kodavanti, U., A. Henriquez, D. Miller, M. Schladweiler, S. Edwards, AND S. Snow. Air pollution and neuroendocrine stress-mediated systemic metabolic and inflammatory response. Society of Toxicology, San Antonio, TX, March 11 - 15, 2018.
Impact/Purpose:
This abstracts presents data summary from past six years research showing that irritant inhaled pollutants induce systemic metabolic and immune effects through the activation of sympathetic adrenal medullary and hypothalamus-pituitary-adrenal axes.
Description:
New experimental evidence involving the role of neuroendocrine activation challenges an accepted mechanistic paradigm of how irritant air pollutants induce systemic metabolic impairment and lung injury/inflammation. We focus on recent air pollution studies highlighting how the release of stress hormones through two fundamental survival mechanisms, the sympathetic-adrenal-medullary and hypothalamus-pituitary-adrenal axes, lead to downstream systemic metabolic imbalance and activation of an innate immune response. Widespread metabolic changes observed after air pollution exposure, typical of a flight-or-fight response, are characterized by adipose lipolysis, muscle protein catabolism, inhibition of pancreatic insulin secretion and increased gluconeogenesis as determined using metabolomic assessment in rodents and humans. There is also evidence of a major metabolic shift in the liver associated with transcriptional depression of lipid catabolism and increased mitochondrial stress. Furthermore, the ozone-induced innate immune response involves extravasation of immune cells to the lung and is associated with changes in stress hormones. The roles of circulating epinephrine and cortisol/corticosterone are examined using interventional approaches involving pharmacological agents specific for adrenergic and glucocorticoid receptors with or without the surgical removal of the whole adrenal glands or adrenal medullas. These studies emphasize that the presence of circulating stress hormones is necessary in mediating irritant air pollutants-induced metabolic and lung inflammatory effects and demonstrate selective modulation based on the differences in the tissue distribution of specific adrenergic and glucocorticoid receptors. Chronic air pollution-induced alterations in homeostatic mechanisms and dysregulated stress response pathways are postulated to contribute to diabetes, obesity and cardiovascular disease susceptibility. (Does not reflect USEPA policy).