Abstract P065: Changes in Lysophosphatidic Acids and Lysophosphatidylcholines with Fish Oil Consumption wnd their Correlates with Platelet Aggregation
Authors: Abdolahi Amir , Brenna J. Thomas , Mousa Shaker , Lawrence Peter , Thevenet-Morrison Kelly , Cai Xueya , Georas Steve , Block Robert C 
Published: July 2021

Background:
Lysophosphatidic acids (LPA) and lysophosphatidylcholines (LPC) are phospholipids, each containing one fatty acid, and have effects on atherogenic mechanisms. No data currently exist regarding the effects of aspirin and fish oil (FO) ingestion on these potent lipid mediators in humans with diabetes mellitus (DM). We hypothesized that ingestion of these agents alter LPA and LPC concentrations and that these effects correlate with platelet function.

Methods:
Using a sequential clinical trial approach, 30 adults with type 2 DM were treated with 81 mg/d of aspirin for 7 days, then with a 28-day regimen of FO (4g/day containing 1600 mg EPA and 800 mg DHA) after which they restarted 81 mg/d of aspirin for another 7 days. After the ingestion of a standard low-fat meal, phlebotomies were performed at baseline, 4 hours and 7 days after the ingestion of aspirin alone, 28 days after FO alone, and 4 hours and 7 days after aspirin and FO ingestion together. Eleven LPCs and 11 LPAs were analyzed using a modified Bligh and Dyer extract of plasma and infusion into an ABI QTrap 2000 via an Advion Nanomate robotic device. Platelet function was measured using whole blood aggregometry and via assays. Changes in concentrations of LPAs and LPCs compared to baseline were assessed using mixed models accounting for statin use, blood draw, BMI, presence of HTN, gender, race, smoking status, alcohol use, fish consumption, and education. Pearson’s correlations (r) were calculated for comparing LPAs and LPCs with platelet function. P-values less than 0.05 were considered statistically significant.

Results:
FO ingestion reduced concentrations of all 11 LPAs, including EPA (20:5n3) and DHA (22:6n3) species. EPA and DHA LPC concentrations significantly increased by FO alone and in combination with aspirin. Stearic acid (18:0) and alpha-linolenic acid (18:3n3) LPCs were significantly reduced by FO combined with aspirin after 4 hours and 7 days. Changes in 18:0 and oleic acid (18:1) LPAs after FO moderately correlated with the platelet aggregation agonist collagen (r=0.41, p=0.02 and r=0.39, p=0.03, respectively) whereas changes in EPA and DHA LPCs did not correlate with platelet aggregation or function. However, EPA changes with FO and aspirin moderately correlated with the platelet aggregation agonist ADP after 4 hours (r=0.46, p=0.01) but not 7 days (r=0.04, p=0.83).

Conclusions:
The ingestion of FO with and without aspirin has significant effects on plasma lysophospholipid levels in subjects with DM. Given the pleiotropic roles of lysophospholipids in platelet function and atherogenesis, these results suggest that the formation of potent lipid mediators- derived from ingested fats- may be more important than the simple ingestion of the fats. Our results should be used to generate new hypotheses applying different phospholipids in the evaluation of atherogenic mechanisms.