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Effect of infusion of "tris-galactosyl-cholesterol" on plasma cholesterol, clearance of lipoprotein cholesteryl esters, and biliary secretion in the rat.

As shown by us previously (van Berkel et al. 1985. J. Biol. Chem. 260: 2694-2699 and van Berkel et al. 1985. J. Biol. Chem. 260: 12203-12207) the clearance of both low density lipoproteins (LDL) and high density lipoproteins (HDL) from the blood can be greatly enhanced by pretreatment of these lipoproteins with a tris-galactosylated cholesterol derivative, which makes these particles recognizable by hepatic galactosyl-receptors. Here we report that intravenous infusion of the (water-soluble) tris-galactosyl-cholesterol in rats caused a dose-dependent decrease of the plasma cholesterol level. This fall was sustained long after termination of the infusion. It was not observed upon infusion of tris-glucosyl-cholesterol. The fall in plasma cholesterol was accompanied by an increase in hepatic cholesterol. Upon injection of rat HDL and LDL labeled in their cholesteryl ester moieties, plasma clearance of label in both lipoproteins was enhanced in rats infused with tris-galactosyl-cholesterol, the stimulation being more pronounced when the label was in HDL. The appearance of label in bile was also enhanced in the rats receiving the compound, again more markedly when the label was given as HDL. Ninety four percent or more of the radioactivity excreted in the bile was in the form of bile salts, with conjugated cholate being the major species in both control and treated rats; 6% or less of the radioactivity in the bile was as free cholesterol. Infusion of tris-galactosyl-cholesterol constitutes a new and defined method of lowering plasma lipoprotein levels by enhancing their uptake in the liver.