tetano
Editor, Senior Moderator
Biochem Biophys Res Commun. 2018 Feb 16. pii: S0006-291X(18)30366-8. doi: 10.1016/j.bbrc.2018.02.135. [Epub ahead of print]
[h=1]Increased mortality from influenza infection in long-chain acyl-CoA dehydrogenase knockout mice.[/h] Shinde A[SUP]1[/SUP], Luo J[SUP]1[/SUP], Bharathi SS[SUP]1[/SUP], Shi H[SUP]1[/SUP], Beck ME[SUP]1[/SUP], McHugh KJ[SUP]1[/SUP], Alcorn JF[SUP]1[/SUP], Wang J[SUP]1[/SUP], Goetzman ES[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] Fatty acid oxidation; Influenza; Long-chain acyl-CoA dehydrogenase; Lung injury
PMID: 29458021 DOI: 10.1016/j.bbrc.2018.02.135
[h=1]Increased mortality from influenza infection in long-chain acyl-CoA dehydrogenase knockout mice.[/h] Shinde A[SUP]1[/SUP], Luo J[SUP]1[/SUP], Bharathi SS[SUP]1[/SUP], Shi H[SUP]1[/SUP], Beck ME[SUP]1[/SUP], McHugh KJ[SUP]1[/SUP], Alcorn JF[SUP]1[/SUP], Wang J[SUP]1[/SUP], Goetzman ES[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] Fatty acid oxidation; Influenza; Long-chain acyl-CoA dehydrogenase; Lung injury
PMID: 29458021 DOI: 10.1016/j.bbrc.2018.02.135