Intestinal cholesterol uptake from phospholipid vesicles and from simple and mixed micelles

This study was undertaken in vitro to examine the rat jejunal uptake of cholesterol from phospholipid vesicles and from mixed bile salt micelles, under conditions of low effective resistance of the intestinal unstirred water layer. Cholesterol uptake, Jd, occurred from vesicles only when the cholesterol:phospholipid ratio was high. The addition of phospholipid (PL) to micelles comprising 20 mM taurodeoxycholic acid (TDC) extended the concentration of cholesterol, beyond which the relationship between cholesterol concentration and uptake remained linear. When the concentration of cholesterol in the bulk phase was held constant and the concentration of TDC or of PL added to the TDC was increased, there was a decline in cholesterol uptake; this effect was masked when the concentration of TDC was high, or when higher concentrations of PL were added to the mixed micelle. When increasing concentrations of palmitic acid were added to mixed micelles composed of cholesterol, TDC and PL, the uptake of cholesterol decreased; in contrast, cholesterol uptake progressively increased when palmitic acid was added to simple TDC micelles. The results suggest that the mechanism responsible for cholesterol uptake may vary, depending on the nature of the constituents of the micelle, and it is proposed that PL inhibits the intestinal uptake of cholesterol by altering the partitioning of cholesterol out of the micelle.