EPA and DHA containing phospholipids have contrasting effects on membrane structure
Omega-3 FAs EPA and DHA influence membrane fluidity, lipid rafts, and signal transduction. A clinical trial, Reduction of Cardiovascular Events with Icosapent Ethyl—Intervention Trial, demonstrated that high-dose EPA (4 g/d icosapent ethyl) reduced composite cardiovascular events in statin-treated h...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227521000882 |
| _version_ | 1819100081761026048 |
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| author | Samuel C.R. Sherratt Rebecca A. Juliano Christina Copland Deepak L. Bhatt Peter Libby R. Preston Mason |
| author_facet | Samuel C.R. Sherratt Rebecca A. Juliano Christina Copland Deepak L. Bhatt Peter Libby R. Preston Mason |
| author_sort | Samuel C.R. Sherratt |
| collection | DOAJ |
| description | Omega-3 FAs EPA and DHA influence membrane fluidity, lipid rafts, and signal transduction. A clinical trial, Reduction of Cardiovascular Events with Icosapent Ethyl—Intervention Trial, demonstrated that high-dose EPA (4 g/d icosapent ethyl) reduced composite cardiovascular events in statin-treated high-risk patients. EPA benefits correlated with on-treatment levels, but similar trials using DHA-containing formulations did not show event reduction. We hypothesized that differences in clinical efficacy of various omega-3 FA preparations could result from differential effects on membrane structure. To test this, we used small-angle X-ray diffraction to compare 1-palmitoyl-2-eicosapentaenoyl-sn-glycero-3-phosphocholine (PL-EPA), 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (PL-DHA), and 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PL-AA) in membranes with and without 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol. Electron density profiles (electrons/Å3 vs. Å) were used to determine membrane structure, including membrane width (d-space). PL-EPA and PL-DHA had similar membrane structures without POPC and/or cholesterol but had contrasting effects in the presence of POPC and cholesterol. PL-EPA increased membrane hydrocarbon core electron density over an area of ±0–10 Å from the center, indicating an extended orientation. PL-DHA increased electron density in the phospholipid head group region, concomitant with disordering in the hydrocarbon core and a similar d-space (58 Å). Adding equimolar amounts of PL-EPA and PL-DHA produced changes that were attenuated compared with their separate effects. PL-AA increased electron density centered ±12 Å from the membrane center. The contrasting effects of PL-EPA, PL-DHA, and PL-AA on membrane structure may contribute to differences observed in the biological activities and clinical actions of various omega-3 FAs. |
| first_indexed | 2024-12-22T00:57:06Z |
| format | Article |
| id | doaj.art-ed2f7c180e724ec48de4021a49614ae7 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-22T00:57:06Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
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| series | Journal of Lipid Research |
| spelling | doaj.art-ed2f7c180e724ec48de4021a49614ae72022-12-21T18:44:17ZengElsevierJournal of Lipid Research0022-22752021-01-0162100106EPA and DHA containing phospholipids have contrasting effects on membrane structureSamuel C.R. Sherratt0Rebecca A. Juliano1Christina Copland2Deepak L. Bhatt3Peter Libby4R. Preston Mason5Elucida Research LLC, Beverly, MA, USA; Department of Molecular, Cellular, and Biomedical Sciences, University of New Hampshire, Durham, NH, USAAmarin Pharma, Inc., Bridgewater, NJ, USAAmarin Pharma, Inc., Bridgewater, NJ, USADepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USADepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USAElucida Research LLC, Beverly, MA, USA; Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; For correspondence: R. Preston Mason.Omega-3 FAs EPA and DHA influence membrane fluidity, lipid rafts, and signal transduction. A clinical trial, Reduction of Cardiovascular Events with Icosapent Ethyl—Intervention Trial, demonstrated that high-dose EPA (4 g/d icosapent ethyl) reduced composite cardiovascular events in statin-treated high-risk patients. EPA benefits correlated with on-treatment levels, but similar trials using DHA-containing formulations did not show event reduction. We hypothesized that differences in clinical efficacy of various omega-3 FA preparations could result from differential effects on membrane structure. To test this, we used small-angle X-ray diffraction to compare 1-palmitoyl-2-eicosapentaenoyl-sn-glycero-3-phosphocholine (PL-EPA), 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (PL-DHA), and 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PL-AA) in membranes with and without 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol. Electron density profiles (electrons/Å3 vs. Å) were used to determine membrane structure, including membrane width (d-space). PL-EPA and PL-DHA had similar membrane structures without POPC and/or cholesterol but had contrasting effects in the presence of POPC and cholesterol. PL-EPA increased membrane hydrocarbon core electron density over an area of ±0–10 Å from the center, indicating an extended orientation. PL-DHA increased electron density in the phospholipid head group region, concomitant with disordering in the hydrocarbon core and a similar d-space (58 Å). Adding equimolar amounts of PL-EPA and PL-DHA produced changes that were attenuated compared with their separate effects. PL-AA increased electron density centered ±12 Å from the membrane center. The contrasting effects of PL-EPA, PL-DHA, and PL-AA on membrane structure may contribute to differences observed in the biological activities and clinical actions of various omega-3 FAs.http://www.sciencedirect.com/science/article/pii/S0022227521000882omega-3 FAsX-ray diffractionmembrane structureeicosapentaenoic aciddocosahexaenoic acidarachidonic acid |
| spellingShingle | Samuel C.R. Sherratt Rebecca A. Juliano Christina Copland Deepak L. Bhatt Peter Libby R. Preston Mason EPA and DHA containing phospholipids have contrasting effects on membrane structure Journal of Lipid Research omega-3 FAs X-ray diffraction membrane structure eicosapentaenoic acid docosahexaenoic acid arachidonic acid |
| title | EPA and DHA containing phospholipids have contrasting effects on membrane structure |
| title_full | EPA and DHA containing phospholipids have contrasting effects on membrane structure |
| title_fullStr | EPA and DHA containing phospholipids have contrasting effects on membrane structure |
| title_full_unstemmed | EPA and DHA containing phospholipids have contrasting effects on membrane structure |
| title_short | EPA and DHA containing phospholipids have contrasting effects on membrane structure |
| title_sort | epa and dha containing phospholipids have contrasting effects on membrane structure |
| topic | omega-3 FAs X-ray diffraction membrane structure eicosapentaenoic acid docosahexaenoic acid arachidonic acid |
| url | http://www.sciencedirect.com/science/article/pii/S0022227521000882 |
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