title: Obesity Increases Mortality and Modulates the Lung Metabolome during Pandemic H1N1 Influenza Virus Infection in Mice.
abstract: Obese individuals are at greater risk for hospitalization and death from infection with the 2009 pandemic H1N1 influenza virus (pH1N1). In this study, diet-induced and genetic-induced obese mouse models were used to uncover potential mechanisms by which obesity increases pH1N1 severity. High-fat diet-induced and genetic-induced obese mice exhibited greater pH1N1 mortality, lung inflammatory responses, and excess lung damage despite similar levels of viral burden compared with lean control mice. Furthermore, obese mice had fewer bronchoalveolar macrophages and regulatory T cells during infection. Obesity is inherently a metabolic disease, and metabolic profiling has found widespread usage in metabolic and infectious disease models for identifying biomarkers and enhancing understanding of complex mechanisms of disease. To further characterize the consequences of obesity on pH1N1 infection responses, we performed global liquid chromatography-mass spectrometry metabolic profiling of lung tissue and urine. A number of metabolites were perturbed by obesity both prior to and during infection. Uncovered metabolic signatures were used to identify changes in metabolic pathways that were differentially altered in the lungs of obese mice such as fatty acid, phospholipid, and nucleotide metabolism. Taken together, obesity induces distinct alterations in the lung metabolome, perhaps contributing to aberrant pH1N1 immune responses.
authors: Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors: J Justin
authors: JJ
authors: Milner
authors: Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors: Jenny
authors: J
authors: Rebeles
authors: Systems and Translational Science Center, RTI International, Research Triangle Park, NC 27709; and.
authors: Suraj
authors: S
authors: Dhungana
authors: Systems and Translational Science Center, RTI International, Research Triangle Park, NC 27709; and.
authors: Delisha A
authors: DA
authors: Stewart
authors: Systems and Translational Science Center, RTI International, Research Triangle Park, NC 27709; and.
authors: Susan C J
authors: SC
authors: Sumner
authors: Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors: Matthew H
authors: MH
authors: Meyers
authors: Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109.
authors: Peter
authors: P
authors: Mancuso
authors: Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; melinda_beck@unc.edu.
authors: Melinda A
authors: MA
authors: Beck
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D005434:Flow Cytometry; D053118:Influenza A Virus, H1N1 Subtype; D008168:Lung / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D009976:Orthomyxoviridae Infections / Q000378:metabolism* / Q000473:pathology*