The Protective Effect of Dietary EPA‐Enriched Ethanolamine Plasmalogens against Hyperlipidemia in Aged Mice

Abstract Decreased ethanolamine plasmalogen (PlsEtn) levels are observed in erythrocytes from patients with hyperlipidemia. Dietary PlsEtns can increase erythrocyte membrane PlsEtns and decrease plasma cholesterol; however, they do not affect triacylglycerol levels. In the present study, the effects of eicosapentaenoic acid‐enriched PlsEtn (EPA‐PlsEtn) on hyperlipidemia are evaluated in comparison to those of EPA‐enriched phosphatidylcholine (EPA‐PC) in senescence‐accelerated mice (SAMP8). The results indicate that EPA‐PlsEtn supplementation dramatically reduces triacylglycerol (42%, p < 0.01) and serum cholesterol (32%, p < 0.05) levels compared to those in the model group, while EPA‐PC treatment does not significantly affect either of these parameters. Mechanistically, the triacylglycerol‐lowering effect of EPA‐PlsEtn may be attributed to accelerated fatty acid β‐oxidation that occurs due to the upregulation of carnitine palmitoyl transferase (CPT)‐1a, CPT‐2, and acyl‐CoA oxidase 1 expression. Additionally, EPA‐PlsEtn supplementation can reduce hepatic cholesterol levels via promoting cholesterol efflux mediated by ATP binding cassette subfamily G member 5 and the synthesis of bile acids regulated by farnesoid X receptor. These findings suggest that EPA‐PlsEtn may be promising for use as a novel therapeutic agent for the treatment of age‐related hyperlipidemia and metabolic disorder. Practical Applications : Supplementary EPA‐PlsEtn can reduce both cholesterol and triacylglycerol levels in the serum and liver of SAMP8 mice, which contributes to the protection against age‐related hyperlipidemia. EPA‐PlsEtn supplementation accelerates hepatic fatty acid β‐oxidation and cholesterol efflux, which results in lowering serum lipid levels. EPA‐PlsEtn and EPA‐PC exert different effects on lipid metabolism via different metabolic pathways, which indicates the activity‐structure relationship is worth further investigation.