Effect of acute ozone exposure on the lung metabolomes of obese and lean mice

• Published in: PloS one Vol. 12; no. 7; p. e0181017
• Main Authors: Mathews, Joel Andrew, Kasahara, David Itiro, Cho, Youngji, Bell, Lauren Nicole, Gunst, Philip Ross, Karoly, Edward D, Shore, Stephanie Ann
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.07.2017; Public Library of Science (PLoS)
• Subjects: Air pollution; Animals; Asthma; Attenuation; Bacteria; Biochemistry; Biology and Life Sciences; Carbohydrate Metabolism; Carbohydrates; Chromatography; Cytokines; Earth Sciences; Ecology and Environmental Sciences; Environmental health; Exposure; Fatty acids; Flushing; Gas chromatography; Gas Chromatography-Mass Spectrometry; Glutathione; Health aspects; Human subjects; Inflammation; Influence; Ligands; Lipid metabolism; Lipid Metabolism - drug effects; Lipids; Lung; Lung - drug effects; Lung - metabolism; Lungs; Mammals; Mass spectrometry; Mass spectroscopy; Medicine and Health Sciences; Metabolism; Metabolites; Metabolome - drug effects; Metabolomics; Mice; Mice, Obese; Obesity; Obesity - complications; Obesity - metabolism; Ozone; Ozone - toxicity; Phosphocholine; Physical Sciences; Pollutants; Public health; Research and Analysis Methods; Rodents; North Carolina; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0181017

Pulmonary responses to the air pollutant, ozone, are increased in obesity. Both obesity and ozone cause changes in systemic metabolism. Consequently, we examined the impact of ozone on the lung metabolomes of obese and lean mice. Lean wildtype and obese db/db mice were exposed to acute ozone (2 ppm for 3 h) or air. 24 hours later, the lungs were excised, flushed with PBS to remove blood and analyzed via liquid-chromatography or gas-chromatography coupled to mass spectrometry for metabolites. Both obesity and ozone caused changes in the lung metabolome. Of 321 compounds identified, 101 were significantly impacted by obesity in air-exposed mice. These included biochemicals related to carbohydrate and lipid metabolism, which were each increased in lungs of obese versus lean mice. These metabolite changes may be of functional importance given the signaling capacity of these moieties. Ozone differentially affected the lung metabolome in obese versus lean mice. For example, almost all phosphocholine-containing lysolipids were significantly reduced in lean mice, but this effect was attenuated in obese mice. Glutathione metabolism was also differentially affected by ozone in obese and lean mice. Finally, the lung metabolome indicated a role for the microbiome in the effects of both obesity and ozone: all measured bacterial/mammalian co-metabolites were significantly affected by obesity and/or ozone. Thus, metabolic derangements in obesity appear to impact the response to ozone.