You are here:
Acute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II Diabetes
Citation:
Snow, S., D. Miller, M. Schladweiler, A. Ledbetter, J. Richards, C. Gordon, AND U. Kodavanti. Acute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II Diabetes. Society of Toxicology, San Diego, CA, March 22 - 26, 2015.
Impact/Purpose:
Mounting evidence indicates an association between air pollution exposure and metabolic disorders such as obesity and type 2 diabetes (T2D. These data indicate that O3 exposure has a profound effect on glucose and lipid metabolism, and that preexisting T2D and diet-induced obesity augments pulmonary injury and metabolic impairment following an acute exposure.
Description:
Abstract for Society of Toxicology, March 22-25, 2015, San Diego, CAAcute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II DiabetesS.J. Snow1,3, D. Miller2, V. Bass2, M. Schladweiler3, A. Ledbetter3, J. Richards3, C. Gordon3, and U. Kodavanti3,21ORISE, RTP, NC2UNC, Chapel Hill, NC3EPA, RTP, NCMounting evidence indicates an association between air pollution exposure and metabolic disorders such as obesity and type 2 diabetes (T2D). We have demonstrated that acute O3 exposures in metabolically normal rats induce hyperglycemia and glucose intolerance. We hypothesize that preexisting T2D and diet-induced obesity will exacerbate pulmonary injury and lead to metabolic impairment following O3 exposure. Male Wistar and Goto-Kakizaki (GK) rats, a lean T2D Wistar-derived model, were fed a normal or high cholesterol atherogenic diet starting at 4 wks of age for 12 wks. Rats were then exposed to air or 1 ppm O3, 6h/day for 1 or 2 days with and without an 18h recovery. GKs expressed progressive hyperglycemia and glucose intolerance at 0, 4, 8, and 12 wks post-diet suggesting an early onset of diet-induced insulin resistance. O3-induced glucose intolerance was noted in Wistars on day 1 while GKs developed further intolerance on day 2. O3-induced hyperglycemia was also evident in GKs regardless of diet. All O3 effects were reversed with an 18h recovery. There were significant increases in triglycerides and cholesterol levels in rats fed the atherogenic diet that were further exacerbated in the GKs following O3 exposure, indicating dyslipidemia. Serum leptin levels were also increased only in GKs, demonstrating O3-induced lipolysis in rats with preexisting T2D. Furthermore, despite having the lowest minute volume, GKs exposed to O3 had the greatest pulmonary damage as indicated by significant increases in several lung injury biomarkers. Collectively, these data indicate that O3 exposure has a profound effect on glucose and lipid metabolism, and that preexisting T2D and diet-induced obesity augments pulmonary injury and metabolic impairment following an acute exposure. These metabolic alterations might arise from neuronal stress mechanisms, and upon longer air pollution exposure, may lead to insulin resistance and accelerated diabetes. (This abstract does not reflect US EPA Policy)