Metabolic profiling uncovers differential metabolic signatures and biomarkers in influenza‐infected obese mice (392.3)

Abstract

Obese individuals are at greater risk for hospitalization and death from influenza virus infection. Paralleling human evidence, obese mice also exhibit greater mortality to influenza compared with lean mice. Although obesity is known to impair immunity, the mechanisms driving greater influenza severity in the obese remain unclear. Therefore, we have taken a novel approach for elucidating the underlying mechanisms contributing to altered infection responses. We conducted metabolic profiling to identify differential metabolic signatures in infected lean and obese mice, and integrated metabolite data with immune parameters to identify significant immune‐metabolic interactions. Urine, feces, serum, bronchoalveolar lavage fluid, lungs, mesenteric white adipose tissue, and livers were harvested from uninfected or influenza infected mice for subsequent 1H NMR‐based metabolic profiling. Multivariate statistical analysis revealed distinct metabolic signatures between lean and obese mice, both locally at the site of infection and systemically. Obesity caused perturbations in lipid, choline, nucleotide and carbohydrate metabolic pathways during infection. Further, activated T cells negatively correlated with 3‐hydroxybutyrate and creatine in the lungs of obese mice, possibly suggesting regulatory functions for these metabolites. Of interest, urine samples obtained from obese mice as early as two days post‐infection had a distinct metabolic signature compared with urine samples from lean infected mice. Given the rapidity of influenza transmission and the sudden onset of symptoms during infection, identification of an early infection metabolic signature and unique biomarkers in a non‐invasive biofluid, such as urine, has widespread prognostic and diagnostic implications. Further, identification of altered metabolic pathways in obese mice will facilitate better understanding of the determinants of greater influenza mortality observed in obese mice and humans.Grant Funding Source: Supported by NORC DK56350