1H NMR-based profiling reveals differential immune-metabolic networks during influenza virus infection in obese mice.
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.
Gillings School of Global Public Health, Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
J Justin
JJ
Milner
Section of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, United Kingdom.
Jue
J
Wang
Gillings School of Global Public Health, Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Patricia A
PA
Sheridan
Section of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, United Kingdom.
Tim
T
Ebbels
Gillings School of Global Public Health, Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Melinda A
MA
Beck
Section of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, United Kingdom.
Jasmina
J
Saric
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D055442:Metabolome; D051379:Mice; D008820:Mice, Obese; D009976:Orthomyxoviridae Infections / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011859:Radiography
D015415:Biomarkers