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Human Ozone (O3) Exposure Alters Serum Profile of Lipid Metabolites
Miller, D., U. Kodavanti, E. Karoly, W. Cascio, AND A. Ghio. Human Ozone (O3) Exposure Alters Serum Profile of Lipid Metabolites. Society of Toxicology, San Diego, CA, March 22 - 26, 2015.
HUMAN OZONE (O3) EXPOSURE ALTERS SERUM PROFILE OF LIPID METABOLITES Miller, D B.1; Kodavanti, U P.2 Karoly, E D.3; Cascio W.E2, Ghio, A J. 21. UNC-Chapel Hill, Chapel Hill, N.C., United States. 2. NHEERL, U.S. EPA, RTP, N.C., United States. 3. METABOLON INC., Durham, N.C., United States.Air pollutants have been linked to insulin resistance (IR) and the rise of cardio-metabolic disease. Yet, pollutant effects on metabolism are poorly understood. We have recently shown in rodents that acute O3 exposure alters systemic metabolic homeostasis likely through a stress response pathway. The goal of this study was to examine if humans exposed to O3 produce similar systemic metabolic alterations. Serum samples were obtained from a clinical study involving O3 exposure of healthy young-adults (18-40 years age, n=24) with no history of drug usage, smoking, or respiratory disease. The crossover study included two clinical visits (each separated by more than two weeks) where each fasted volunteer was blindly exposed to either FA or 0.3 ppm O3 for 2hrs during intermittent exercise. A metabolomic approach used UPLC-MS/MS and GC-MS to profile metabolites in serum collected immediately after exposure. O3 exposure significantly increased serum lysolipids, monoacylglycerol, glycerol, and medium and long chain free fatty acids (FFA; C12-C20) likely from adipose lypolysis. O3 also elevated metabolites of sphingolipids involved in the transport of lipids and may consequently increase FFAs in the liver. Ketone body (3-hydroxybutyrate) and acylcatinitines associated with fatty acid β-oxidation increased significantly. O3-induced increases in dicarboxylic acids, azelate and 2-hydroxyglutarate might indicate a shift to fatty acid ω-oxidation. Increases in n3 and n6 PUFAs may stimulate inflammatory processes upon longer O3 exposure. Importantly, doubling of the cortisol levels by O3 supports the hypothesis that systemic metabolic alterations after O3 are induced via a stress response through hypothalamic-pituitary-adrenal axis activation. Altogether, the metabolomic analysis reveals hyperlipidemia and increases in metabolites reflecting activated lipid catabolism associated with increases in stress hormones in O3 exposed humans. Longer exposures might contribute to IR and metabolic disease. (Does not reflect the EPA Policy).
This study shows that ozone exposure increases circulating fatty acids, fatty acid catabolites and a stress hormone, cortisol in humans.
URLs/Downloads:MILLER 2015 SOT ABSTRACT-UK10-6-14.DOCX
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH