Year: 2021
Type: article
Abstract: 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/Å 3 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.
Source: Journal of Lipid Research
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: American Heart Association, Cleveland Clinic, CSL Behring, Boston VA Research Institute, Amarin Corporation, MyoKardia, Regado Biosciences, Belvoir Media Group, Novo Nordisk, St. Jude Medical, Amarin Pharma, National Heart, Lung, and Blood Institute, Duke Clinical Research Institute, Daiichi Sankyo Europe
OpenAlex ID: W3192792201