Influence of class B scavenger receptors on cholesterol flux across the brush border membrane and intestinal absorption.
To learn more about how the step of cholesterol uptake into the brush border membrane (BBM) of enterocytes influences overall cholesterol absorption, we measured cholesterol absorption 4 and 24 h after administration of an intragastric bolus of radioactive cholesterol in mice with scavenger receptor class B, type 1 (SR-BI) and/or cluster determinant 36 (CD36) deleted. The cholesterol absorption efficiency is unaltered by deletion of either one or both of the receptors. In vitro determinations of the cholesterol uptake specific activity of the BBM from the mice reveal that the scavenger receptors facilitate cholesterol uptake into the proximal BBM. It follows that cholesterol uptake into the BBM is not normally rate-limiting for the cholesterol absorption process in vivo; a subsequent step, such as NPC1L1-mediated transfer from the BBM into the interior of the enterocyte, is rate-limiting. The absorption of dietary cholesterol after 4 h in mice lacking SR-BI and/or CD36 and fed a high-fat/high-cholesterol diet is delayed to more distal regions of the small intestine. This effect probably arises because ATP binding cassette half transporters G5 and G8-mediated back flux of cholesterol from the BBM to the lumen of the small intestine limits absorption and causes the local cholesterol uptake facilitated by SR-BI and CD36 to become rate-limiting under this dietary condition.
Nguyen
David V
DV
Gastroenterology, Hepatology, and Nutrition Division, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4318, USA.
Drover
Victor A
VA
Knopfel
Martin
M
Dhanasekaran
Padmaja
P
Hauser
Helmut
H
Phillips
Michael C
MC
D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D001692:Biological Transport; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002250:Carbon Radioisotopes; D002784:Cholesterol / Q000378:metabolism*; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism; D008074:Lipoproteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008871:Microvilli / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*
C462600:ABCG5 protein, mouse; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters; D018955:CD36 Antigens; D002250:Carbon Radioisotopes; D008074:Lipoproteins; D026901:Membrane Transport Proteins; C482445:Npc1l1 protein, mouse; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol