The objectives of this research are (a) to systemmatically assess the site(s) at which, and the mechanism by which, the intestine discriminates between absorbable and nonabsorbable sterols; and (b) to determine the mechanisms of the hypocholesteremic effects of plant and marine sterols. Studies are designed both in vitro and in vivo to investigate three potential sites of discrimination: - The intralumenal phase to evaluate differences in, and competition between sterols, for distribution between the oil, micellar and monomolecular phases of sterols during absorption. - The mucosal transport barriers including the roles of the unstirred water layer, the surface-associated mucins and cholesterol esterase. These studies include conditions modulating unidirectional transport of sterols into the intestinal mucosa. - The cellular phase including: the role of sterol carrier proteins in intracellular sterol transport; the relative roles mucosal cholesterol esterase and acyl CoA: cholesterol acyl transferase (ACAT) in esterification of intracellular sterols; and differential distribution of sterols (free and esterified) between the chylomicron membrane and core lipids. Determination of overall absorbability of, and competition between sterols, is assessed by analysis of mesenteric lymph for mass, esterification and lipoprotein distribution of sterols.
