A comparative study of sterol absorption in different small-intestinal brush border membrane models

Abstract

We reported previously that the absorption of cholesterol and long-chain cholesteryl esters by rabbit small-intestinal brush border membranes (BBMV) is protein-mediated (Thurnhofer, H., and H. Hauser. 1990. Biochemistry. 29:2142-2148; Compassi, S., M. Werder, D. Boffelli, F. E. Weber, H. Hauser, and G. Schulthess. 1995. Biochemistry. 34: 16473-16482). Evidence is presented for similar cholesterol transport activities in rabbit, pig, and human BBMV. As BBMV are subject to a number of limitations and the influence of these on sterol absorption is unknown, it is desirable to verify results obtained with this model system in other brush border membrane models more closely related to the in vivo situation. Sterol absorption in intact enterocytes parallels the absorption measured in BBMV, provided that both model systems are normalized to equal sucrase activity. The parallel behavior of the two brush border membrane models lends support to our previous conclusion that the brush border membrane takes up free and esterified cholesterol in a facilitated and energy-independent process. The absorption of sterols in small-intestinal segments mounted in the Ussing chamber is shown to be a complex process in which the diffusion of the bile salt micelles to the brush border membrane is rate-limiting. All brush border membrane models share the disadvantage of being unstable and subject to degradation. The seriousness of the problem increases apparently with the complexity of the model, i.e., in the order BBMV–>enterocytes–>intestinal segments. One main conclusion of this study is that no brush border membrane model is sufficient and satisfactory, therefore conclusive work in lipid absorption can never be based on a single brush border membrane model.