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The Journal of Lipid Research, Vol. 39, 1197-1209, June 1998
Copyright © 1998 by Lipid Research, Inc.

Original Article

Phospholipase A₂ relieves phosphatidylcholine inhibition of micellar cholesterol absorption and transport by human intestinal cell line Caco-2¹

Correspondence to: Reynold Homan.

Cholesterol absorption from bile acid micelles is suppressed by phosphatidylcholine (PC) in the micelles. The effects of micellar phospholipid composition on absorption, metabolism, and secretion of lipids were examined in Caco-2 cells incubated with micelles composed of taurocholic acid, cholesterol, oleic acid, monooleoylglycerol, and phospholipid. Significant amounts of all micelle lipids were absorbed from micelles lacking phospholipid. Cholesterol absorption was accompanied by cholesterol esterification and secretion. Micellar oleic acid was also absorbed and reesterified primarily into triacylglycerol which was also secreted. Lipid absorption and secretion from micelles containing lysophosphatidylcholine (LPC) were similar to that obtained with phospholipid-free micelles. LPC was also extensively absorbed. In contrast, incubations with PC-containing micelles resulted in large reductions in the absorption, esterification, and secretion of cholesterol without significant decreases in oleic acid absorption, conversion to acylated lipids, or triacylglycerol secretion. A relatively small reduction in monoacylglycerol absorption from PC-containing micelles was detected. Retinol absorption was not affected by micellar PC. Substitution of LPC for half or more of the PC reversed the PC-dependent decrease in cholesterol absorption. Pancreatic phospholipase A₂ (pPLA₂) enhanced cholesterol absorption from PC-containing micelles. The pPLA₂-dependent increase in cholesterol absorption was inhibited by the pPLA₂ inhibitor FPL 67047XX.

The results indicate micellized cholesterol absorption by enterocytes is uniquely dependent on the elimination of micellar phosphatidylcholine and thus directly dependent on the lipolytic action of pancreatic phospholipase A₂ (pPLA₂). Consequently, pPLA₂ inhibitors may be a new and novel class of cholesterol absorption inhibitors for therapeutic use.—Homan, R., and K. L. Hamelehle. Phospholipase A₂ relieves phosphatidylcholine inhibition of micellar cholesterol absorption and transport by human intestinal cell line Caco-2. J. Lipid Res. 1998. 39: 1197–1209.

Supplementary key words: enterocyte, micelle, bile acid, phospholipid, monoacylglycerol, triacylglycerol, fatty acid, lysophosphatidylcholine, retinol, FPL 67047XX

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