1H NMR-Based Profiling Reveals Differential Immune-Metabolic Networks during Influenza Virus Infection in Obese Mice

• Published in: PloS one Vol. 9; no. 5; p. e97238
• Main Authors: Milner, J. Justin, Wang, Jue, Sheridan, Patricia A., Ebbels, Tim, Beck, Melinda A., Saric, Jasmina
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2014; Public Library of Science (PLoS)
• Subjects: Adipose tissue; Alveoli; Amino acids; Animal models; Animals; Bacterial infections; Biology and Life Sciences; Biomarkers; Biomarkers - metabolism; Bronchus; Cancer; Carbohydrates; Choline; Diagnostic systems; Disease; Epidemics; Feces; Gene expression; Humans; Hypotheses; Infections; Infectious diseases; Influenza; Influenza A; Influenza A Virus, H1N1 Subtype - metabolism; Laboratory animals; Liver; Lungs; Magnetic resonance; Magnetic Resonance Imaging; Medicine; Metabolic networks; Metabolic pathways; Metabolic syndrome; Metabolites; Metabolome; Mice; Mice, Obese; NMR; Nuclear magnetic resonance; Nutrition; Obesity; Orthomyxoviridae Infections - diagnostic imaging; Orthomyxoviridae Infections - metabolism; Oxidative stress; Pandemics; Pathogenesis; Public health; Radiography; Research and Analysis Methods; Rodents; Signatures; Surgery; Swine flu; Urine; Viruses; Vitamin C; North Carolina; United Kingdom > UK; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0097238

Obese individuals are at greater risk for death from influenza virus infection. Paralleling human evidence, obese mice are also more susceptible to influenza infection mortality. However, the underlying mechanisms driving greater influenza severity in the obese remain unclear. Metabolic profiling has been utilized in infectious disease models to enhance prognostic or diagnostic methods, and to gain insight into disease pathogenesis by providing a more global picture of dynamic infection responses. Herein, metabolic profiling was used to develop a deeper understanding of the complex processes contributing to impaired influenza protection in obese mice and to facilitate generation of new explanatory hypotheses. Diet-induced obese and lean mice were infected with influenza A/Puerto Rico/8/34. 1H nuclear magnetic resonance-based metabolic profiling of urine, feces, lung, liver, mesenteric white adipose tissue, bronchoalveolar lavage fluid and serum revealed distinct metabolic signatures in infected obese mice, including perturbations in nucleotide, vitamin, ketone body, amino acid, carbohydrate, choline and lipid metabolic pathways. Further, metabolic data was integrated with immune analyses to obtain a more comprehensive understanding of potential immune-metabolic interactions. Of interest, uncovered metabolic signatures in urine and feces allowed for discrimination of infection status in both lean and obese mice at an early influenza time point, which holds prognostic and diagnostic implications for this methodology. These results confirm that obesity causes distinct metabolic perturbations during influenza infection and provide a basis for generation of new hypotheses and use of this methodology in detection of putative biomarkers and metabolic patterns to predict influenza infection outcome.