EPA-enriched ethanolamine plasmalogen alleviates atherosclerosis via mediating bile acids metabolism

The possible underlying mechanism involved in the alleviation of dietary EPA-enriched ethanolamine plasmalogen (EPA-PlsEtn) on atherosclerosis. Administration with EPA-PlsEtn promoted excess cholesterol to synthesize bile acids via increasing CYP7A1 expression. Increased TMCAs might attribute to the suppression of FXR expression to further enhance the CYP7A1 transcription. [Display omitted] •EPA-PlsEtn dramatically reduced atherosclerotic lesions and serum LDL-c levels.•EPA-PlsEtn increased excess cholesterol excrete into feces as bile acid.•EPA-PlsEtn altered bile acids profile and further suppressed FXR expression. The DHA/EPA enriched ethanolamine plasmalogens (EPA-PlsEtn) are widely present in seafood, and EPA-PlsEtn exhibits unique effects on improving cognitive functions. However, there were no reports on the alleviation of dietary EPA-PlsEtn on atherosclerosis. In the present study, supplementation with EPA-PlsEtn for 8 weeks dramatically reduced atherosclerotic lesions by 78% and serum LDL-c levels by 73.9% compared with model group. EPA-PlsEtn possessed lowest hepatic cholesterol levels associated with increased bile acids synthesis and excretion into feces. EPA-PlsEtn increased CYP7A1 expression through suppressing FXR activation. The increased proportion of bile acid TMCA, FXR antagonist, might contribute to the increased bile acid synthesis. In conclusion, different with EPA in form of EE or PC, EPA-PlsEtn efficiently alleviated atherosclerosis via lowering cholesterol levels by suppressing FXR expression. These findings provided new evidence and thought to explain the unique bioactivity of EPA-PlsEtn and new sight to re-understand the structure-activities relationship of DHA/EPA.