Impaired beta-oxidation increases vulnerability to influenza A infection.
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Authors
van Liempd, SebastiaanCabrera, Diana
Pilzner, Carolin
Kollmus, Heike
Schughart, Klaus

Falcón-Pérez, Juan M
Issue Date
2021-10-09
Metadata
Show full item recordAbstract
Influenza A virus (IAV) infection casts a significant burden on society. It has particularly high morbidity and mortality rates in patients suffering from metabolic disorders. The aim of this study was to relate metabolic changes with IAV susceptibility using well-characterized inbred mouse models. We compared the highly susceptible DBA/2J (D2) mouse strain for which IAV infection is lethal with the C57BL/6J (B6) strain, which exhibits a moderate course of disease and survives IAV infection. Previous studies showed that D2 has higher insulin and glucose levels and is predisposed to develop diet-induced type 2 diabetes. Using high-resolution liquid chromatography-coupled MS, the plasma metabolomes of individual animals were repeatedly measured up to 30 days postinfection. The biggest metabolic difference between these strains in healthy and infected states was in the levels of malonylcarnitine, which was consistently increased 5-fold in D2. Other interstrain and intrastrain differences in healthy and infected animals were observed for acylcarnitines, glucose, branched-chain amino acids, and oxidized fatty acids. By mapping metabolic changes to canonical pathways, we found that mitochondrial beta-oxidation is likely disturbed in D2 animals. In noninfected D2 mice, this leads to increased glycerolipid production and reduced acylcarnitine production, whereas in infected D2 animals, peroxisomal beta-oxidation becomes strongly increased. From these studies, we conclude that metabolic changes caused by a distortion of mitochondrial and peroxisomal metabolism might impact the innate immune response in D2, leading to high viral titers and mortality.Citation
J Biol Chem. 2021 Oct 9;297(5):101298. doi: 10.1016/j.jbc.2021.101298. Epub ahead of print.Publisher
Elsevier/ASMBMPubMed ID
34637789Type
ArticleLanguage
enEISSN
1083-351Xae974a485f413a2113503eed53cd6c53
10.1016/j.jbc.2021.101298
Scopus Count
The following license files are associated with this item:
- Creative Commons
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