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Papers In Press, published online ahead of print April 21, 2004
J. Lipid Res., doi:10.1194/jlr.M400030-JLR200
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Department of Medicine, Gastroenterology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215
Corresponding Author: dqwang{at}caregroup.harvard.edu
In the present study, we investigated whether intestinal sterol efflux transporters Abcg5 and Abcg8 play a major role in determining variations in cholesterol absorption efficiency, and compared the physiological functions of the duodenal, jejunal, and ileal Abcg5 and Abcg8 on the absorption of cholesterol and sitostanol in inbred mice challenged with various amounts of cholesterol, sitostanol, hydrophilic or hydrophobic bile acids. We found that Abcg5 and Abcg8 in the jejunum and ileum, but not in the duodenum, were main determinants in determining, in part, variations in cholesterol absorption efficiency. The jejunal and ileal Abcg5 and Abcg8 played a major regulatory role in response to high dietary cholesterol and were more sensitive in the regulation of cholesterol absorption compared with sitostanol absorption. These results, combined with different sterol uptake rates, suggest that the absorption efficiency of cholesterol and sitostanol is determined by the net results between influx and efflux of intraluminal cholesterol and sitostanol molecules cross the apical membrane of the enterocyte. Hydrophilic and hydrophobic bile acids influenced cholesterol absorption through mediating cholesterol solubilization and its physical-chemical state within the small intestinal lumen. We conclude that cholesterol absorption is mainly regulated by the jejunal and ileal Abcg5 and Abcg8 in mice.
Revised on March 29, 2004
Accepted on April 8, 2004
Cholesterol absorption is mainly regulated by the jejunal and ileal ATP-binding cassette sterol efflux transporters Abcg5 and Abcg8 in mice
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