title: Transient and persistent metabolomic changes in plasma following chronic cigarette smoke exposure in a mouse model.
abstract: Cigarette smoke exposure is linked to the development of a variety of chronic lung and systemic diseases in susceptible individuals. Metabolomics approaches may aid in defining disease phenotypes, may help predict responses to treatment, and could identify biomarkers of risk for developing disease. Using a mouse model of chronic cigarette smoke exposure sufficient to cause mild emphysema, we investigated whether cigarette smoke induces distinct metabolic profiles and determined their persistence following smoking cessation. Metabolites were extracted from plasma and fractionated based on chemical class using liquid-liquid and solid-phase extraction prior to performing liquid chromatography mass spectrometry-based metabolomics. Metabolites were evaluated for statistically significant differences among group means (p-value≤0.05) and fold change ≥1.5). Cigarette smoke exposure was associated with significant differences in amino acid, purine, lipid, fatty acid, and steroid metabolite levels compared to air exposed animals. Whereas 60% of the metabolite changes were reversible, 40% of metabolites remained persistently altered even following 2 months of smoking cessation, including nicotine metabolites. Validation of metabolite species and translation of these findings to human plasma metabolite signatures induced by cigarette smoking may lead to the discovery of biomarkers or pathogenic pathways of smoking-induced disease.
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado School of Medicine, Denver, Colorado, United States of America.
authors.forename: Charmion I
authors.initials: CI
authors.lastname: Cruickshank-Quinn
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado School of Medicine, Denver, Colorado, United States of America; Department of Pharmacology, School of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Spencer
authors.initials: S
authors.lastname: Mahaffey
authors.affiliation: Departments of Medicine and of Biochemistry and Molecular Biology, Indiana University, Indianapolis, Indiana, United States of America.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Justice
authors.affiliation: Department of Biostatistics and Informatics, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Grant
authors.initials: G
authors.lastname: Hughes
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado School of Medicine, Denver, Colorado, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Armstrong
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado, United States of America.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Bowler
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado School of Medicine, Denver, Colorado, United States of America; Department of Pediatrics, National Jewish Health, Denver, Colorado, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Reisdorph
authors.affiliation: Departments of Medicine and of Biochemistry and Molecular Biology, Indiana University, Indianapolis, Indiana, United States of America; Richard L. Roudebush VA Medical Center, Indianapolis, Indiana, United States of America.
authors.forename: Irina
authors.initials: I
authors.lastname: Petrache
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado School of Medicine, Denver, Colorado, United States of America.
authors.forename: Nichole
authors.initials: N
authors.lastname: Reisdorph
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000737:chemistry; D004195:Disease Models, Animal; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D011656:Pulmonary Emphysema / Q000097:blood* / Q000139:chemically induced; D012907:Smoking / Q000009:adverse effects*
chemical_list: D015415:Biomarkers