Abstract
Background
Oxylipins are formed from oxidation of omega-6 (n6) and omega-3 (n3) fatty acids (FAs). Evidence for inflammatory effects comes mostly from adults.
Methods
Oxylipins from n6 FA (27 n6-oxylipins) and n3 FA (12 n3-oxylipins) were measured through ultra-high-performance liquid chromatography–mass spectrometry (LC-MS/MS) in plasma from 111 children at risk of type 1 diabetes (age 1–17 years) studied longitudinally. Oxylipin precursor FAs (arachidonic acid, linoleic acid, alpha-linolenic acid, docosahexaenoic acid, eicosapentaenoic acid) were measured in red blood cell (RBC) membrane and plasma. Precursor FAs dietary intake was measured through food frequency questionnaire and environmental tobacco smoke (ETS) through questionnaires. Linear mixed models were used to test oxylipins with predictors.
Results
Age associated with 15 n6- and 6 n3-oxylipins; race/ethnicity associated with 3 n6- and 1 n3-oxylipins; sex associated with 2 n6-oxylipins. ETS associated with lipoxin-A4. Oxylipins associated with precursor FAs in plasma more often than RBC. RBC levels and dietary intake of precursor FAs more consistently associated with n3-oxylipins than with n6-oxylipins.
Conclusions
In healthy children, oxylipin levels change with age. Oxylipins associated with precursor FAs more often in plasma than RBC or diet, suggesting that inflammatory regulation leading to FA release into plasma may also be a determinant of oxylipin generation.
Impact
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This is the first study to examine predictors of oxylipins in healthy children at risk of type 1 diabetes.
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In healthy children at risk of type 1 diabetes, many oxylipins change with age, and most oxylipins do not differ by sex or race/ethnicity.
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Environmental tobacco smoke exposure was associated with the presence of lipoxin A4.
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Omega-6- and omega-3-related oxylipin levels were consistently associated with their respective precursor fatty acid levels measured in the plasma.
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Proportionally more omega-3 compared to omega-6 oxylipins were associated with dietary intake and red blood cell membrane levels of the respective precursor fatty acid.
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Acknowledgements
This work was supported by the National Institutes of Health R01-DK104351 and R01-DK32493.
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T.B. designed the study, performed data analysis, interpreted the data, and drafted the manuscript. J.M.N. designed the study, interpreted the data, and edited the manuscript. B.C.D. and O.F. collected data and reviewed and edited the manuscript. L.A.V., R.K.J., P.M.C., J.S., K.W., M.C.-S. F.D., and M.R. reviewed and edited the manuscript.
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Patient consent was required for this study. All study recruitment and protocols designed to protect participants enrolled in the parent study, DAISY, were approved by the Colorado Multiple Institutional Review Board. All participants provided written informed consent.
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Buckner, T., Vanderlinden, L.A., Johnson, R.K. et al. Predictors of oxylipins in a healthy pediatric population. Pediatr Res 89, 1530–1540 (2021). https://doi.org/10.1038/s41390-020-1084-2
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DOI: https://doi.org/10.1038/s41390-020-1084-2
