Abstract
The abundance of docosahexaenoic acid (DHA) in phospholipids in the brain and retina has generated interest to search for its role in mediating neurological functions. Besides the source of many oxylipins with pro-resolving properties, DHA also undergoes peroxidation, producing 4-hydroxyhexenal (4-HHE), although its function remains elusive. Despite wide dietary consumption, whether supplementation of DHA may alter the peroxidation products and their relationship to phospholipid species in brain and other body organs have not been explored sufficiently. In this study, adult mice were administered a control or DHA-enriched diet for 3 weeks, and phospholipid species and peroxidation products were examined in brain, heart, and plasma. Results demonstrated that this dietary regimen increased (n-3) and decreased (n-6) species to different extent in all major phospholipid classes (PC, dPE, PE-pl, PI and PS) examined. Besides changes in phospholipid species, DHA-enriched diet also showed substantial increases in 4-HHE in brain, heart, and plasma. Among different brain regions, the hippocampus responded to the DHA-enriched diet showing significant increase in 4-HHE. Considering the pro- and anti-inflammatory pathways mediated by the (n-6) and (n-3) polyunsaturated fatty acids, unveiling the ability for DHA-enriched diet to alter phospholipid species and lipid peroxidation products in the brain and in different body organs may be an important step forward towards understanding the mechanism(s) for this (n-3) fatty acid on health and diseases.
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Data Availability
Original data for the manuscript are available upon written request of the corresponding author.
Abbreviations
- 4-HHE:
-
4-Hydroxyhexenal
- 4-HNE:
-
4-Hydroxynonenal
- ARA:
-
Arachidonic acid
- CHD:
-
1,3-Cyclohexanedione
- cPLA2:
-
Cytosolic phospholipases A2
- CTL:
-
Control
- DHA:
-
Docosahexaenoic acid
- HO-1:
-
Heme oxygenase-1
- HPLC:
-
High performance liquid chromatography
- iPLA2:
-
Ca+2-independent phospholipases A2
- LC–MS/MS:
-
Liquid chromatography-mass spectrometry/mass spectrometry
- MS:
-
Mass spectrometry
- Nrf2:
-
Nuclear factor erythroid 2-related factor 2
- PBS:
-
Phosphate-buffered saline
- PC:
-
Phosphatidylcholine
- PE:
-
Phosphatidylethanolamine
- dPE:
-
Diacyl-phosphatidylethanolamine
- PE-p1:
-
Alkenylacyl-phosphatidylethanolamine or phosphatidylethanolamine plasmalogen
- PI:
-
Phosphatidylinositol
- PL:
-
Phospholipids
- PLA2:
-
Phospholipases A2
- PS:
-
Phosphatidylserine
- PUFA:
-
Polyunsaturated fatty acid
- UHPLC:
-
Ultra-high performance liquid chromatography
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Funding
This study is supported by the MU Research Council grant (17–009) and support from Department of Radiology Mission Enhancement funds from University of Missouri to DQB, and NIH/NIA RF1 AG061872 to XH. We wish to thank DSM Nutritional Products (USA) for donating DHASCO, the source of dietary DHA used in this study. MC’s visit to University of Missouri was funded in part by a scholarship for young scientists from the Polish Academy of Sciences and Mossakowski Medical Research Centre, Poland.
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GYS, CMG, XH, DB, and BY conceived the idea, RL, JC, MA, MC, and TW carried out the animal study and analysis of lipid peroxidation products. CQ, MP, and XH carried out the methodology and analysis of phospholipid species. GYS, MA, XH, CMG wrote the original draft, and KLF, ZG, MW, AA, and DB reviewed and edited the manuscript. All authors agreed and participated in preparation of the manuscript.
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All experiments were approved by the University of Missouri Animal Care and Use Committee (#8945) and were performed in compliance with the National Institutes of Health (NIH) guidelines for the Care and Use of Laboratory Animals.
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Sun, G.Y., Appenteng, M.K., Li, R. et al. Docosahexaenoic Acid (DHA) Supplementation Alters Phospholipid Species and Lipid Peroxidation Products in Adult Mouse Brain, Heart, and Plasma. Neuromol Med 23, 118–129 (2021). https://doi.org/10.1007/s12017-020-08616-0
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DOI: https://doi.org/10.1007/s12017-020-08616-0