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Biochem Biophys Res Commun. 2018 Mar 4;497(2):700-704. doi: 10.1016/j.bbrc.2018.02.135. Epub 2018 Feb 16.

Increased mortality from influenza infection in long-chain acyl-CoA dehydrogenase knockout mice.

Author information

1
Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, United States.
2
Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, United States. Electronic address: eric.goetzman@chp.edu.

Abstract

We previously showed that the mitochondrial fatty acid oxidation enzyme long-chain acyl-CoA dehydrogenase (LCAD) is expressed in alveolar type II pneumocytes and that LCAD-/- mice have altered breathing mechanics and surfactant defects. Here, we hypothesized that LCAD-/- mice would be susceptible to influenza infection. Indeed, LCAD-/- mice demonstrated increased mortality following infection with 2009 pandemic influenza (A/CA/07/09). However, the mortality was not due to increased lung injury, as inflammatory cell counts, viral titers, and histology scores all showed non-significant trends toward milder injury in LCAD-/- mice. To confirm this, LCAD-/- were infected with a second, mouse-adapted H1N1 virus (A/PR/8/34), to which they responded with significantly less lung injury. While both strains become increasingly hypoglycemic over the first week post-infection, LCAD-/- mice lose body weight more rapidly than wild-type mice. Surprisingly, while acutely fasted LCAD-/- mice develop hepatic steatosis, influenza-infected LCAD-/- mice do not. They do, however, become more hypothermic than wild-type mice and demonstrate increased blood lactate values. We conclude that LCAD-/- mice succumb to influenza from bioenergetic starvation, likely due to increased reliance upon glucose for energy.

KEYWORDS:

Fatty acid oxidation; Influenza; Long-chain acyl-CoA dehydrogenase; Lung injury

PMID:
29458021
PMCID:
PMC5850965
DOI:
10.1016/j.bbrc.2018.02.135
[Indexed for MEDLINE]
Free PMC Article

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