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CHOLESTEROL ABSORPTION AND TRANSINTESTINAL CHOLESTEROL EFFLUX (TICE) RATES ARE UNALTERED IN MICE OVEREXPRESSING INTESTINAL SR-BI.

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abstract
It has recently been shown that reverse cholesterol transport (RCT) does not rely solely on biliary secretion (37), but also involves the direct excretion of cholesterol by the proximal small intestine through a process known as trans-intestinal cholesterol efflux (TICE). There is almost no information in literature regarding molecular mechanisms regulating TICE. It has long been known that scavenger receptor class B type I (SR-BI) plays a crucial role in RCT in the liver by facilitating selective uptake of high density lipoprotein (HDL) cholesterol. Interestingly, SR-BI is also expressed in the small intestine. Previously it has been reported that mice overexpressing SR-BI specifically in the proximal small intestine have accelerated cholesterol absorption (83). In contrast, we hypothesized that over expression of SR-B1 would augment the TICE pathway by facilitating intestinal clearance of plasma cholesterol. To test this hypothesis a series of experiments were conducted by using mice transgenically overexpressing SR-BI in the proximal small intestine (SR-BIInt.-Tg) in the presence or absence of biliary cholesterol contributions either on a low (0.015%) or high (0.2%) (wt/wt) cholesterol diet. As previously reported, SR-BIInt.-Tg mice had significantly lower plasma cholesterol levels. However, in contrast to previous reports, SR-B1Int.-Tg mice had unaltered fractional cholesterol absorption and fecal neutral sterol excretion rates. Our results suggest that SR-BI is not rate-limiting for intestinal cholesterol absorption or fecal neutral sterol loss through the TICE pathway in mice. Therefore, additional studies are required to identify intestinal lipoprotein receptors involved the delivery of plasma cholesterol to the intestine for TICE pathway.
subject
atherosclerosis
cholesterol
HDL
LDL
reverse cholesterol transport
TICE
contributor
Bura, Kanwardeep Singh (author)
Brown, Mark J (committee chair)
Dawson, Paul A (committee member)
Parks, John S (committee member)
Rudel, Lawrence L (committee member)
Temel, Ryan E (committee member)
date
2012-01-18T09:35:30Z (accessioned)
2012-01-18T09:35:30Z (available)
2011 (issued)
degree
Molecular Pathology (discipline)
identifier
http://hdl.handle.net/10339/36430 (uri)
language
en (iso)
publisher
Wake Forest University
title
CHOLESTEROL ABSORPTION AND TRANSINTESTINAL CHOLESTEROL EFFLUX (TICE) RATES ARE UNALTERED IN MICE OVEREXPRESSING INTESTINAL SR-BI.
type
Thesis

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