TY - JOUR
T1 - Fish Oil Supplementation Modifies the Proteome, Lipidome, and Function of High-Density Lipoprotein
T2 - Findings from a Trial in Young Healthy Adults
AU - Mueller, Paul A.
AU - Bergstrom, Paige
AU - Rosario, Sara
AU - Heard, Melissa
AU - Pamir, Nathalie
N1 - Publisher Copyright:
© 2024 American Society for Nutrition
PY - 2024/4
Y1 - 2024/4
N2 - Background: Fish 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. Objectives: We aimed to determine if 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 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. Results: Following 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 (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 (R2 = 0.7353; P = 0.014) and interleukin 6 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.
AB - Background: Fish 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. Objectives: We aimed to determine if 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 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. Results: Following 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 (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 (R2 = 0.7353; P = 0.014) and interleukin 6 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.
KW - cardiovascular disease
KW - high-density lipoprotein
KW - lipidomics
KW - omega-3 fatty acids
KW - proteomics
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U2 - 10.1016/j.tjnut.2024.01.007
DO - 10.1016/j.tjnut.2024.01.007
M3 - Article
C2 - 38237669
AN - SCOPUS:85184757256
SN - 0022-3166
VL - 154
SP - 1130
EP - 1140
JO - Journal of Nutrition
JF - Journal of Nutrition
IS - 4
ER -