scholarly journals Oxylipin metabolism is controlled by mitochondrial β-oxidation during bacterial inflammation

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Mariya Misheva ◽  
Konstantinos Kotzamanis ◽  
Luke C. Davies ◽  
Victoria J. Tyrrell ◽  
Patricia R. S. Rodrigues ◽  
...  

AbstractOxylipins are potent biological mediators requiring strict control, but how they are removed en masse during infection and inflammation is unknown. Here we show that lipopolysaccharide (LPS) dynamically enhances oxylipin removal via mitochondrial β-oxidation. Specifically, genetic or pharmacological targeting of carnitine palmitoyl transferase 1 (CPT1), a mitochondrial importer of fatty acids, reveal that many oxylipins are removed by this protein during inflammation in vitro and in vivo. Using stable isotope-tracing lipidomics, we find secretion-reuptake recycling for 12-HETE and its intermediate metabolites. Meanwhile, oxylipin β-oxidation is uncoupled from oxidative phosphorylation, thus not contributing to energy generation. Testing for genetic control checkpoints, transcriptional interrogation of human neonatal sepsis finds upregulation of many genes involved in mitochondrial removal of long-chain fatty acyls, such as ACSL1,3,4, ACADVL, CPT1B, CPT2 and HADHB. Also, ACSL1/Acsl1 upregulation is consistently observed following the treatment of human/murine macrophages with LPS and IFN-γ. Last, dampening oxylipin levels by β-oxidation is suggested to impact on their regulation of leukocyte functions. In summary, we propose mitochondrial β-oxidation as a regulatory metabolic checkpoint for oxylipins during inflammation.

2020 ◽  
Author(s):  
Mariya Misheva ◽  
Konstantinos Kotzamanis ◽  
Luke C Davies ◽  
Victoria J Tyrrell ◽  
Patricia R S Rodrigues ◽  
...  

AbstractOxylipins are potent mediators requiring strict control. How they are removed en masse during infection/inflammation is unknown. Herein, lipopolysaccharide (LPS) dynamically increased their mitochondrial β-oxidation, impacting leukocyte bioactivity. Genetic/pharmacological targeting of CPT1 showed <50 oxylipins were robustly removed by macrophage mitochondria during inflammation in vitros and in vivo. Stable isotope-lipidomics demonstrated secretion-reuptake recycling for 12-HETE and its intermediate metabolites. Oxylipin β-oxidation was uncoupled from oxidative phosphorylation. Transcriptional interrogation of human neonatal sepsis revealed significant upregulation of many candidates, encoding proteins for mitochondrial uptake and β-oxidation of long-chain fatty acyls (ACSL1,3,4, ACADVL, CPT1B, CPT2, HADHB). ACSL1/Acsl1 upregulation was a signature in multiple human/murine macrophage datasets. In summary, mitochondrial β-oxidation is a regulatory metabolic checkpoint for oxylipins during infection. This has implications for patients with CPT1 deficiency, at higher risk of mortality during respiratory infections. We propose that mitochondrial β-oxidation capacity to remove oxylipins during infection may directly influence development of inflammation.


2011 ◽  
Vol 70 (OCE3) ◽  
Author(s):  
C. J. Harden ◽  
A. N. Jones ◽  
T. Maya-Jimenez ◽  
M. E. Barker ◽  
N. J. Hepburn ◽  
...  

1997 ◽  
Vol 1997 ◽  
pp. 129-129
Author(s):  
M.D. Carro ◽  
E.L. Miller ◽  
O.C. Fabb

In one in vitro study Ashes et al. (1992) reported that C20 and C22 fatty acids (FA) from fish oil were not hydrogenated to any significant extent by rumen microorganisms. However, to our knowledge, no measurement on hydrogenation has been performed on fishmeal (FM) FA. The aim of this experiment was to study the in vivo and in situ rumen hydrogenation of long-chain FA of two different FM: FMl (60 g FA/g DM) and FM2 (85 g FA/g DM).Six sheep fitted with rumen cannulae and single duodenal cannulae were fed every 2 hours, receiving 1 kg/d of a 60:40 hay:concentrate diet, either alone (Control; C) or supplemented with 40 g FM/d (FMl and FM2). The experiment was carried out over four periods (two sheep received one of the diets in each period) and Cr-NDF was used as a marker to estimate duodenal flow. Data were subjected to analysis of variance using the ANOVA procedure of the Statistical Analysis Systems (SAS, 1994).


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