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The Role of Underlying Type 2 Diabetes Mellitus and Obesity in Ozone-Induced Pulmonary Injury and Metabolic Impairment
Citation:
Snow, S., D. Miller (Johnson), V. Bass, M. Schladweiler, A. Ledbetter, J. Richards, D. Andrews, C. Gordon, AND U. Kodavanti. The Role of Underlying Type 2 Diabetes Mellitus and Obesity in Ozone-Induced Pulmonary Injury and Metabolic Impairment. Presented at American Thoracic Society, San Diego, CA, May 16 - 21, 2014.
Impact/Purpose:
Diabetes is a risk factor for air pollution induced pulmonary and systemic toxicity. This research demonstrates that a rat model of human type 2 diabetes is more susceptible to ozone induced metabolic impairment and lung injury than healthy rats.
Description:
RATIONALE: A growing body of evidence indicates an association between air pollution exposure and metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). We have recently demonstrated that an acute exposure to ozone in metabolically normal rat strains produces hyperglycemia and glucose intolerance. In this study, we hypothesize that preexisting T2DM and diet-induced obesity will exacerbate metabolic impairment and adverse pulmonary effects following an acute ozone exposure. METHODS: Male Wistar and Goto-Kakizaki (GK) rats, a lean T2DM inbred model derived from Wistars, were fed a normal or high-cholesterol atherogenic diet starting at 4 wks of age for 12 wks. Body composition measurements and glucose tolerance testing (GTT) were conducted before the start of the diet and every 4 wks thereafter. Twelve wks after the initial start of the diet, rats were exposed to filtered air or 1.0 ppm ozone, 6h/day for 1 or 2 consecutive days with and without an 18h recovery period. GTT testing was conducted immediately following each exposure and after the 18h recovery. Lung lavage, blood, and tissues were collected to further assess pulmonary injury and metabolic impairment. RESULTS: Body composition analysis indicated that Wistars had significantly greater body weight and lower body fat percentage than the GKs. In addition, the high-cholesterol atherogenic diet caused a significant increase in body weight and body fat percentage starting 8 and 4 wks post-diet, respectively, in both strains. GTT testing illustrated that GK rats had significantly elevated hyperglycemia and glucose intolerance at 0, 4, 8, and 12 wks post-diet. Furthermore, GKs, but not Wistars, fed the high-cholesterol atherogenic diet had a significant increase in glucose intolerance 4, 8, and 12 wks post-diet. There were temporal differences in ozone-induced glucose intolerance: Wistars developed intolerance on day 1 while GKs developed intolerance on day 2. In each case, this ozone effect was reversed after an 18h recovery period. In addition, baseline blood glucose levels were significantly elevated only in GK rats following a 1 or 2 day ozone exposure regardless of diet. We also observed significant increases in several lung injury biomarkers including total protein, albumin, lactate dehydrogenase, and N-acetyl glucosaminidase following a 1 and 2 day ozone exposure in both strains with levels being further exacerbated in the GKs. CONCLUSIONS: These data indicate that preexisting T2DM, but not diet-induced obesity, augments metabolic impairment and pulmonary injury following an ozone exposure. (This abstract does not reflect the US EPA Policy).