8(R)-hydroxy-eicosapentaenoic acid (8R-HEPE) induces transcription of cholesterol efflux receptors via activation of liver X receptor in macrophages.

Abstract

Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular disease. 8-HEPE from North Pacific krill (Euphausia pacifica) is known to reduce plasma LDL cholesterol levels and increase plasma HDL cholesterol levels in LDL receptor knock-out mice fed a western diet. Moreover, 8-HEPE also reduces the area of aortic atherosclerosis in apoE knock-out mice fed the same diet. In this study, we examined the stereochemical specific activity of 8-HEPE for inducing expression of cholesterol efflux receptors (Abca1 and Abcg1) in J774.1 cells. Our findings show 8R-HEPE induces the expression of Abca1 and Abcg1 via activation of liver X receptor, whereas 8S-HEPE elicits no such activity. These results suggest that 8R-HEPE derived from North Pacific krill may have beneficial effects against dyslipidemia.