Intestinal cholesterol transport proteins: An update and beyond

Research Centre, CHU-Sainte-Justine, Québec, Canada.
Current Opinion in Lipidology (Impact Factor: 5.66). 07/2007; 18(3):310-8. DOI: 10.1097/MOL.0b013e32813fa2e2
Source: PubMed


Various studies have delineated the causal role of dietary cholesterol in atherogenesis. Strategies have thus been developed to minimize cholesterol absorption, and cholesterol transport proteins found at the apical membrane of enterocytes have been extensively investigated. This review focuses on recent progress related to various brush-border proteins that are potentially involved in alimentary cholesterol transport.
Molecular mechanisms responsible for dietary cholesterol and plant sterol uptake have not been completely defined. Growing evidence, however, supports the concept that several proteins are involved in mediating intestinal cholesterol transport, including SR-BI, NPC1L1, CD36, aminopeptidase N, P-glycoprotein, and the caveolin-1/annexin-2 heterocomplex. Other ABC family members (ABCA1 and ABCG5/ABCG8) act as efflux pumps favoring cholesterol export out of absorptive cells into the lumen or basolateral compartment. Several of these cholesterol carriers influence intracellular cholesterol homeostasis and are controlled by transcription factors, including RXR, LXR, SREBP-2 and PPARalpha. The lack of responsiveness of NPC1L1-deficient mice to ezetimibe suggests that NPC1L1 is likely to be the principal target of this cholesterol-lowering drug.
The understanding of the role, genetic regulation and coordinated function of proteins mediating intestinal cholesterol transport may lead to novel ways of treating cardiovascular disease.

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    • "Following food consumption, zebrafish accumulate cytoplasmic lipid drops (LD) in their enterocytes (Walters, unpublished). From there, fats are likely burned via oxidative pathways in the mitochondria or peroxisomes or packaged into chylomicrons , which are secreted from the basolateral surface of enterocytes into lymphatic or blood vessels (Field, 2001; Levy et al., 2007). In chickens, chylomicron production and secretion is highly conserved, with the exception that lipoproteins are secreted from the intestine directly into the portal vein and thus are termed portomicrons (Bensadoun and Rothfeld, 1972; Griffin et al., 1982). "
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    ABSTRACT: Lipids serve essential functions in cells as signaling molecules, membrane components, and sources of energy. Defects in lipid metabolism are implicated in a number of pandemic human diseases, including diabetes, obesity, and hypercholesterolemia. Many aspects of how fatty acids and cholesterol are absorbed and processed by intestinal cells remain unclear and present a hurdle to developing approaches for disease prevention and treatment. Numerous studies have shown that the zebrafish is an excellent model for vertebrate lipid metabolism. In this chapter, we review studies that employ zebrafish to better understand lipid signaling and metabolism.
    Methods in cell biology 01/2011; 101:111-41. DOI:10.1016/B978-0-12-387036-0.00005-0 · 1.42 Impact Factor
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    • "Recent studies have revealed that bile acids are ligands of several nuclear hormone receptors involved in regulating bile acid synthesis, transport, and cholesterol metabolism. The cholesterol pool is derived from two major sources: the synthesis of cholesterol by the liver and the absorption of cholesterol from the intestine [11]. The cholesterol pool rarely changes much because cholesterol input is approximately balanced by cholesterol output via factors such as excretion in bile/feces, skin excretion, and steroid hormone synthesis [12]. "
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    Cholesterol 06/2010; 2010(3):272731. DOI:10.1155/2010/272731
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    • "The ABCA1 protein is expressed in the basolateral membrane of enterocytes, where it effluxes cholesterol from enterocytes for the production of high density lipoprotein [6, 7]. The role of ABCA1 in transporting cholesterol to the intestinal lumen is still unclear because of conflicting data from different studies [7], and its location on the basolateral surface of enterocytes is different from ABCG5 and ABCG8. "
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    Journal of nutrition and metabolism 01/2010; 2010. DOI:10.1155/2010/415075
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