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Inhaled Ozone (O3)-Induces Changes in Serum Metabolomic and Liver Transcriptomic Profiles in Rats
Citation:
Miller, D., E. Karoly, J. Jones, William O. Ward, B. Vallanat, Deborah Andrews, M. Schladweiler, S. Snow, V. Bass, J. Richards, Andy Ghio, W. Cascio, A. Ledbetter, AND U. Kodavanti. Inhaled Ozone (O3)-Induces Changes in Serum Metabolomic and Liver Transcriptomic Profiles in Rats. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 286(2):65-69, (2015).
Impact/Purpose:
Air pollution is recently linked to insulin resistance. In this study we show that the inhaled pulmonary irritant, O3, is able to induce systemic metabolic changes, as seen by hyperglycemia, glucose intolerance, leptinemia, increased serum FFA, cholesterol, and BCAA together with varied changes in liver transcriptome expression involving glucose, protein and lipid metabolism.
Description:
Air pollution has been linked to increased incidence of diabetes. Recently, we showed that ozone (03) induces glucose intolerance, and increases serum leptin and epinephrine in Brown Norway rats. In this study, we hypothesized that 03 exposure will cause systemic changes in metabolic homeostasis and that serum metabolomic and liver transcriptomic profiling will provide mechanistic insights. In the firstexperiment, male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or 03 at 0.25,0.50, or 1.0 ppm, 6 h/day for two days to establish concentration-related effects on glucose tolerance and lung injury. In a second experiment, rats were exposed to FA or 1.0 ppm 03, 6 h day for either one or two consecutive days, and systemic metabolic responses were determined immediately after or 18 h post-exposure. 03 increased serum glucose and leptin on day 1. Glucose intolerance persisted through two days of exposure but reversed 18 h-post second exposure. 03 increased circulating metabolites or glycolysis, long-chain freefatty acids, branched-chain amino acids and cholesterol, while 1,5-anhydroglucitol, bile acids and metabolites of TCA cycle were decreased, indicating impaired glycem1c control, proteolysis and lipolysis. Liver gene expression increased for markers of glycolysis. TCA cycle and gluconeogenes1s, and decreased for markers of steroid and rat biosynthesis. Genes involved in apoptosis and mitochondrial function were also impacted by 03. In conclusion, short-term 03 exposure induces global metabolic derangement involving glucose, lipid, and amino acid metabolism, typical of a stress-response. It remains to be examined if these alterations contribute to insulin resistance upon chronic exposure.
