Class B scavenger receptor-mediated intestinal absorption of dietary beta-carotene and cholesterol.
There is now a general consensus that the intestinal absorption of water-insoluble, dietary lipids is protein-mediated, but the assignment of protein(s) to this function is still a matter of debate. To address this issue, we measured beta-carotene and cholesterol absorption in wild-type and SR-BI knockout mice and the uptake of these lipids in vitro using brush border membrane (BBM) vesicles. From the comparison of the in vivo and in vitro results we conclude that both BBM-resident class B scavenger receptors, SR-BI and CD36, can facilitate the absorption of beta-carotene and cholesterol. SR-BI is essential for beta-carotene absorption, at least in mice on a high fat diet. This is due to the fact that the absorption of beta-carotene is restricted to the duodenum and SR-BI is the predominant receptor in the mouse duodenum. In contrast, SR-BI may be involved but is not essential for cholesterol absorption in the small intestine. The question of whether SR-BI contributes to cholesterol absorption in vivo is still unresolved. Transfection of COS-7 cells with SR-BI or CD36 confers on these cells lipid uptake properties closely resembling those of enterocytes and BBM vesicles. Both scavenger receptors facilitate the uptake of dietary lipids such as beta-carotene, free and esterified cholesterol, phospholipids, and fatty acids into COS-7 cells. This lipid uptake is effected from three different lipid donor particles: mixed bile salt micelles, phospholipid small unilamellar vesicles, and trioleoylglycerol emulsions which are all likely to be present in the small intestine. Ezetimibe, a representative of a new class of drugs that inhibit intestinal cholesterol absorption, blocks SR-BI- and CD36-facilitated uptake of cholesterol into COS-7 cells.
van Bennekum
Ariëtte
A
Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4318, USA.
Werder
Moritz
M
Thuahnai
Stephen T
ST
Han
Chang-Hoon
CH
Duong
Phu
P
Williams
David L
DL
Wettstein
Philipp
P
Schulthess
Georg
G
Phillips
Michael C
MC
Hauser
Helmut
H
D000821:Animal Feed; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage; D001384:Azetidines / Q000008:administration & dosage; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D019556:COS Cells; D002522:Chlorocebus aethiops; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000069438:Ezetimibe; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects / Q000235:genetics; D007421:Intestine, Small / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008871:Microvilli / Q000378:metabolism; D011817:Rabbits; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D014162:Transfection; D019207:beta Carotene / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000924:Anticholesteremic Agents; D001384:Azetidines; D018955:CD36 Antigens; D002791:Cholesterol, Dietary; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D019207:beta Carotene; D000069438:Ezetimibe