Micellar lipid composition profoundly affects LXR-dependent cholesterol transport across CaCo2 cells

Abstract 

Intraluminal phospholipids affect micellar solubilization and absorption of cholesterol. We here study cholesterol transport from taurocholate–phospholipid–cholesterol micelles to CaCo2 cells, and associated effects on ABC-A1 mediated cholesterol efflux. Micellar incorporation of egg-yolk-phosphatidylcholine markedly increased apical retention of the sterol with decreased expression of ABC-A1, an effect that is prevented by synthetic liver X receptor (LXR) or retinoid X receptor (RXR) agonists. On the other hand, incorporation of lyso-phosphatidylcholine (LysoPC) increased ABC-A1–HDL-dependent basolateral cholesterol efflux, an effect that is abated when LXR is silenced. Thus, the modulation of cholesterol metabolism via intraluminal phospholipids is related to the activity of the oxysterol nuclear receptor LXR.

Abbreviations: ABC, ATP-binding casette, DMEM, Dulbecco’s minimum essential medium, FCS, fetal calf serum, HDL, high density lipoprotein, LysoPC, Lyso-phosphatidylcholine, LXR, liver X receptor, NPC1L1, Niemann-Pick C1-like-1, PC, Phosphatidylcholine, RXR, retinoid X receptor, SM, sphingomyelin, TC, taurocholate

Keywords: ABC-A1, Liver X receptor, Bile salt, Intestine, Lyso-phosphatidylcholine, Phosphatidylcholine