Fish Oil Supplementation Modifies the Proteome, Lipidome, and Function of High-Density Lipoprotein: Findings from a Trial in Young Healthy Adults.

backgroundFish oil with the ω-3 fatty acids EPA and DHA is an FDA-approved treatment of patients with severe hypertriglyceridemia. Furthermore, EPA is an FDA-approved treatment of patients with high risk of cardiovascular disease (CVD); however, the cardioprotective mechanisms are unclear.

objectivesWe aimed to determine if fish oil supplementation is cardioprotective due to beneficial modifications in HDL particles.

methodsSeven fish oil naïve subjects without a history of CVD were recruited to take a regimen of fish oil (1125 mg EPA and 875 mg DHA daily) for 30 d, followed by a 30-d washout period wherein no fish oil supplements were taken. HDL isolated from fasting whole blood at each time point via 2-step ultracentrifugation (ucHDL) was assessed for proteome, lipidome, cholesterol efflux capacity (CEC), and anti-inflammatory capacity.

resultsFollowing fish oil supplementation, the HDL-associated proteins immunoglobulin heavy constant γ1, immunoglobulin heavy constant α1, apolipoprotein D, and phospholipid transfer protein decreased compared to baseline (P < 0.05). The HDL-associated phospholipid families sphingomyelins, phosphatidylcholines, and phosphatidylserines increased after fish oil supplementation relative to baseline (P < 0.05). Compared to baseline, fish oil supplementation increased serum HDL's CEC (P = 0.002). Fish oil-induced changes (Post compared with Baseline) in serum HDL's CEC positively correlated with plasma EPA levels (R

conclusionsOverall, fish oil supplementation improved HDL's sterol efflux capacity through comprehensive modifications to its proteome and lipidome.