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Ozone-Induced Metabolic Impairment is Attenuated in Adrenalectomized Wistar Kyoto Rats
Citation:
Miller, D., J. Richards, D. Andrews, V. Bass, S. Snow, M. Schladweiler, A. Ledbetter, AND U. Kodavanti. Ozone-Induced Metabolic Impairment is Attenuated in Adrenalectomized Wistar Kyoto Rats. Presented at American Thoracic Society Meeting, San Diego, CA, May 16 - 21, 2014.
Impact/Purpose:
This research examined metabolic impairment following ozone exposure and shows that ozone metabolic effects are mediated by hormones released from adrenal glands likely through activation of neuronal pathway.
Description:
Rationale: Air pollutants have been linked to increased incidence of metabolic syndrome however the mechanisms are poorly understood. We have recently shown that ozone exposure induces significant hyperglycemia together with elevated serum leptin and epinephrine in the Wistar Kyoto (WKY) rats, suggesting that neurohumoral mediators may be responsible for the ozone-induced metabolic impairment. In this study, we hypothesize that the adrenal gland hormones are essential and contribute to these ozone-induced metabolic effects. Recent studies have shown that ozone can activate the hypothalamic-pituitary-adrenal axis (HPA), which is essential for maintaining metabolic homeostasis through a stress response. Methods: Our objective was to examine the contribution of adrenal-derived neurohormones in ozone-induced pulmonary injury, glucose intolerance, and systemic metabolic impairment. Male WKY rats (11 week old) underwent sham-operation or bilateral adrenalectomy (BA), thus removing further secretion of glucocorticoids, mineralcorticoids, and catecholamines. BA rats were provided water supplemented with 0.9% sodium chloride to maintain salt balance. Within a week of surgery, sham or BA rats were exposed to filtered air or 0.5 ppm ozone, 6h/day for 1 or 2 consecutive days. To determine the duration ozone-mediated metabolic impairment, glucose tolerance testing (GTT) was performed at 0hr or 18hr post- exposure. At necropsy, lung lavage was preformed and serum and tissues were collected to further assess pulmonary injury and metabolic biomarkers. Results: Ozone exposure resulted in hyperglycemia and glucose intolerance in sham-operated rats. In contrast, these effects were significantly reduced in ozone-exposed BA rats. Furthermore, after ozone exposure, serum triglycerides were decreased only in sham-operated but not BA rats. In sham operated rats, ozone resulted in lung injury as determined by analysis of BALF for protein leakage. However, BALF protein and albumin were abnormally elevated in BA rats exposed to air; with no further increase detected in ozone-exposed rats. Conclusion: In this study, we demonstrate that adrenal-derived hormones may contribute to ozone-induced derangement of glucose metabolism. We further show that steroidal and/or chatecholeminergic mediators are necessary in maintaining normal lung vascular integrity and that the inability to generate a typical stress response attenuates ozone-induced hyperglycemia and glucose intolerance. Focused studies are in progress to identify differential contribution of steroidal and catecholeminergic mediators in exacerbation of cardiometabolic disease caused by air pollutants. (This abstract does not reflect the US EPA Policy).