Citation:

Colonna, C., A. Henriquez, J. House, Jon Corton, S. Snow, M. Schladweiler, P. Kodavanti, AND U. Kodavanti. The influence of acute ozone exposure and hepatic vagotomy on glucose and fatty acid metabolism. Society of Toxicology-Virtual, Anaheim, CA, March 15 - 19, 2020.

Impact/Purpose:

This study examines the role of parasympathetic innervation in mediating ozone induced metabolic alterations and shows that although vagus nerve may be involved in insulin secretion, most liver metabolic effects of ozone are only modestly affected by hepatic vagus nerve section.

Description:

Air pollution exposure has been linked to augmented incidences of metabolic diseases like obesity and insulin resistance. We have previously shown that acute ozone (O3) exposure is associated with increased circulating stress hormones and impaired glucose and fatty acid metabolism. In a previous study, Affymetrix array data indicated 2335 genes changed after ozone exposure in healthy rats. Comparing these gene expression changes to a database of ~10K microarray comparisons from chemical exposure in rat liver demonstrated that ozone induced a set of glucocorticoid receptor-regulated genes, indicating the contribution of increased hypothalamic-pituitary-adrenal axis activation after ozone exposure. The aim of this study was to 1) characterize ozone-induced metabolic changes in the liver and 2) determine if these effects are altered by hepatic vagotomy that would reduce parasympathetic influence on metabolic processes. Male 12-week old Wistar-Kyoto (WKY) rats underwent sham surgery or hepatic vagotomy 4-6 days prior to air or ozone exposure (0.0, or 1.0 ppm; 6 hrs/day for 1 or 2 days). Glucose tolerance testing was performed immediately following the first day of ozone exposure, and circulating metabolic hormones and lipids were measured in the serum at both time points. Ozone induced hyperglycemia, glucose intolerance, and increased circulating cholesterol, triglycerides, and leptin were sustained in vagotomized rats. Hepatic vagotomy did decrease circulating insulin on ozone exposed rats only. Liver global gene expression changes were determined using Illumina RNA-sequencing in sham and vagotomized rats. Inhibition of cholesterol biosynthetic genes after ozone exposure in healthy rats suggested suppression of SREBP2 consistent with increases in circulating cholesterol in ozone-exposed rats. In conclusion, ozone induced metabolic alterations were correlated with hepatic glucocorticoid activation and vagus denervation exerted a modest influence on ozone-induced metabolic effects (This abstract does not necessarily reflect US EPA policy).

Record Details: