Fish oil supplementation modifies the proteome, lipidome and function of high-density lipoprotein: Findings from a trial in young healthy adults

J Nutr. 2024 Jan 16:S0022-3166(24)00026-9. doi: 10.1016/j.tjnut.2024.01.007. Online ahead of print.

ABSTRACT

BACKGROUND: Fish oil with the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is an FDA approved treatment for patients with severe hypertriglyceridemia. Further, EPA is an FDA approved treatment for patients with high risk of cardiovascular disease (CVD); however, the cardioprotective mechanisms are not clear. We hypothesized that fish oil supplementation is cardioprotective due to beneficial modifications in HDL particles.

METHODS: Seven fish oil naïve subjects without a history of CVD were recruited to take a regiment of fish oil (1,125mg EPA and 875mg DHA daily) for 30 days, followed by a 30-day washout period wherein no fish oil supplements were taken. HDL isolated from fasting whole blood at each time point via two-step ultracentrifugation (ucHDL) was assessed for proteome, lipidome, cholesterol efflux capacity (CEC), and anti-inflammatory capacity.

RESULTS: Following fish oil, the HDL-associated proteins: immunoglobulin heavy constant gamma 1 (IGHG1), immunoglobulin heavy constant alpha 1 (IGHA1), apolipoprotein D (APOD) and phospholipid transfer protein (PLTP) 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 vs. Baseline) in serum HDL’s CEC positively correlated with plasma EPA levels (R2=0.7256; P=0.015). Similarly, fish oil-induced changes in ucHDL’s CEC positively correlated with ucHDL’s ability to reduce interleukin 10 (IL10) (R2=0.7353; P=0.014) and interleukin 6 (IL6) mRNA expression (R2=0.6322; P=0.033) in a human macrophage cell line.

CONCLUSIONS: Overall, fish oil supplementation improved HDL’s sterol efflux capacity through comprehensive modifications to its proteome and lipidome.

PMID:38237669 | DOI:10.1016/j.tjnut.2024.01.007