Influence of class B scavenger receptors on cholesterol flux across the brush border membrane and intestinal absorption

Gastroenterology, Hepatology, and Nutrition Division, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4318, USA.
The Journal of Lipid Research (Impact Factor: 4.42). 06/2009; 50(11):2235-44. DOI: 10.1194/jlr.M900036-JLR200
Source: PubMed


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.

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Available from: Padmaja Dhanasekaran, Jan 15, 2016
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    • "In a second step, lipids are absorbed by the apical brush border membrane (BBM), through a partially understood mechanism which has strong evidence to be protein-mediated. The scavenger receptors CD36 and SR-BI contributes to the apical uptake of FA or FC [4], [5], [6], [7], [8], [9] whereas NPC1L1 (Niemann-Pick C1-Like 1 protein) is crucial for the absorption of cholesterol but not FA [9], [10], [11]. After absorption, lipids are addressed from the plasma membrane to the endoplasmic reticulum (ER), through a mechanism which involves FA-binding proteins (FABP) but certainly also NPC1L1 [12], [13], [14]. "
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    • "One possibility is that CD36, a fatty acid transporter, may contribute to fatty acid absorption in the small intestine [25]. However, CD36 KO mice showed unaltered intestinal fatty acid uptake, except for the very long chain fatty acids [40], [41]. A decreased chylomicron secretion with a subsequent delay in fat absorption was observed in CD36 KO mice [42]. "
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    • "TG are then re-synthesized in enterocytes and assembled into chylomicrons (CM) which, together with other lipophilic compounds, including the sterols, are released via lymph vessels into the blood circulation [9]. Uptake of dietary cholesterol into epithelial cells involves the Niemann-Pick C1 Like Protein 1 (NPC1L1), the target of the cholesterol-lowering drug ezetimibe [10-12], and possibly the scavenger receptor class B1 (SR-B1) and CD36 [13]. Cholesterol, like other dietary sterols, can also be exported back from the enterocyte into the lumen by the ATP-binding cassette sub-family G member 5 and 8 proteins (ABCG5 and -8) [14]. "
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