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Ozone Induces Glucose Intolerance and Systemic Metabolic Effects in Young and Aged Brown Norway Rats
Bass, V., C. Gordon, K. Jarema, R. MacPhail, W. Cascio, P. Phillips, A. Ledbetter, M. Schladweiler, D. Andrews, D. Johnson, D. Doerfler, AND U. Kodavanti. Ozone Induces Glucose Intolerance and Systemic Metabolic Effects in Young and Aged Brown Norway Rats. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 273(3):551-560, (2013).
Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone could impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in very young and aged rats. Brown Norway (BN) rats, 1,4, 12, and 24 months old were exposed to ozone at 0, 0.25 or 1.Oppm, 6h/day for 2 days (acute) or 2d/week for 13 weeks (subchronic). Additionally, 4 month old rats were exposed to 0 or 1.Oppm ozone, 6h/day for 1 or 2 days (time-course). Glucose tolerance tests occurred immediately after exposure in all studies. Serum and tissue biomarkers were analyzed 18h after final ozone for acute and subchronic studies, and immediately after each day in time-course study. Age-related glucose intolerance, and increases in metabolic biomarkers were apparent at baseline. Acute ozone caused glucose intolerance and hyperglycemia in rats of all ages. Ozone-induced glucose intolerance was reduced in rats exposed for 13 weeks. Acute, but not subchronic ozone increased a2-macrcglobulin, adiponectin and osteopontin. Time-course analysis indicated hyperglycemia at day 1, glucose intolerance at days 1 and 2 (2>1), and a recovery 18h post ozone. Leptin increased day 1 and epinephrine at all times after ozone. Ozone tended to decrease pIRS in liver and adipose tissues. ER stress markers were reduced at day I but increased day 2. In conclusion, age-related metabolic impairments occur in a healthy aging BN rats. More importantly, acute ozone exposure is associated with marked impairment of glucose homeostasis, likely through the sympathetic hormones such as epinephrine.
Recently ambient particulate matter has been linked to increased diabetes and obesity, however the contribution of ozone to metabolic disease outcome is not known.We report that 03 produces acute metabolic alterations characterized by impaired glucose homeostasis and modest impairment of peripheral insulin sensitivity regardless of age. These metabolic alterations are not likely mediated by circulating cytokines, acute phase proteins or liver ER stress. Rather, neurohumoral sympathetic modulation might be important in metabolic effects in rodents. Although advanced age is associated with impaired glucose homeostasis and likely insulin resistance, 03 metabolic effects are only slightly exacerbated in geriatric rats.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH