Ozone modifies the metabolic and endocrine response to glucose: Reproduction of effects with the stress hormone corticosterone
- DOI
- Language of the publication
- English
- Date
- 2018-01-31
- Type
- Article
- Author(s)
- Thomson, Errol M.
- Pilon, Shinjini
- Guénette, Josée
- Williams, Andrew
- Holloway, Alison C.
- Publisher
- Elsevier
Abstract
Air pollution is associated with increased incidence of metabolic disease (e.g. metabolic syndrome, obesity, diabetes); however, underlying mechanisms are poorly understood. Air pollutants increase the release of stress hormones (human cortisol, rodent corticosterone), which could contribute to metabolic dysregulation. We assessed acute effects of ozone, and stress axis involvement, on glucose tolerance and on the metabolic (triglyceride), endocrine/energy regulation (insulin, glucagon, GLP-1, leptin, ghrelin, corticosterone), and inflammatory/endothelial (TNF, IL-6, VEGF, PAI-1) response to exogenous glucose. Male Fischer-344 rats were exposed to clean air or 0.8 ppm ozone for 4 h in whole body chambers. Hypothalamic-pituitary-adrenal (HPA) axis involvement in ozone effects was tested through subcutaneous administration of the glucocorticoid synthesis inhibitor metyrapone (50 mg/kg body weight), corticosterone (10 mg/kg body weight), or vehicle (40% propylene glycol) prior to exposure. A glucose tolerance test (2 g/kg body weight glucose) was conducted immediately after exposure, with blood samples collected at 0, 30, 60, 90, and 120 min. Ozone exposure impaired glucose tolerance, an effect accompanied by increased plasma triglycerides but no impairment of insulin release. Ozone diminished glucagon, GLP-1, and ghrelin responses to glucose, but did not significantly impact inflammatory/endothelial analytes. Metyrapone reduced corticosterone but increased glucose and triglycerides, complicating evaluation of the impact of glucocorticoid inhibition. However, administration of corticosterone reproduced the profile of ozone effects, supporting a role for the HPA axis. The results show that ozone-dependent changes in glucose tolerance are accompanied by altered metabolic and endocrine responses to glucose challenge that are reproduced by exogenous stress hormone.
Plain language summary
Health Canada is responsible for conducting risk assessments on air pollution as part of the Clean Air Regulatory Agenda. Recent research indicates that air pollution may increase the incidence of metabolic diseases such as type 2 diabetes, but underlying mechanisms remain unclear. Health Canada has shown that exposure of rats to common air pollutants like ground-level ozone (a component of smog) and airborne particles can increase stress hormones. Chronically high levels of stress hormones are thought to be involved in the development of metabolic diseases. This study was designed to assess effects of ozone on the body’s response to glucose, as this has been shown to be an early and sensitive indicator of metabolic problems. To do this, Health Canada and McMaster University collaborated on a study in which effects of glucose administration were assessed in rats exposed to air or ozone. Ozone impaired clearance of glucose from the blood (an indicator of metabolic dysfunction), and altered the response of blood factors involved in glucose metabolism. The stress hormone corticosterone reproduced effects of ozone. The results of this study indicate that ozone modifies how the body responds to glucose in a manner similar to stress hormones. The findings contribute to our understanding of health effects of air pollution in the human population.
Subject
- Health,
- Health and safety