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Originally published In Press as doi:10.1194/jlr.M600165-JLR200 on August 26, 2006

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Journal of Lipid Research, Vol. 47, 2374-2381, November 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Rapid transient absorption and biliary secretion of enantiomeric cholesterol in hamsters

Emily J. Westover1,*, Xiaobo Lin1,{dagger}, Terrence E. Riehl§, Lina Ma{dagger}, William F. Stenson§, Douglas F. Covey* and Richard E. Ostlund, Jr.2,{dagger}

* Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110
{dagger} Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110
§ Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110

Published, JLR Papers in Press, August 26, 2006.

1 E. J. Westover and X. Lin contributed equally to this work.

2 To whom correspondence should be addressed. e-mail: rostlund{at}im.wustl.edu

To probe the pathway and specificity of cholesterol absorption, the synthetic enantiomer of cholesterol (ent-cholesterol) and cholesterol were labeled with deuterium, gavaged into hamsters, and measured by negative ion mass spectrometry. Initial uptake of both tracers into the intestinal mucosa at 30 min was similar but cholesterol was temporarily retained there, whereas mucosal ent-cholesterol declined rapidly with concomitantly increased enrichment in both the systemic circulation and the gut lumen. In a 3 day fecal recovery study, ent-cholesterol was quantitatively recovered in the stool, whereas cholesterol absorption was 53.2%. ent-Cholesterol given by intracardiac injection was selectively secreted into bile, and the ratio of ent-cholesterol to cholesterol tracers in the gut lumen increased down the length of the small bowel, with the largest value being found in stool. ent-Cholesterol is efficiently taken up by the intestinal mucosa and undergoes transient enterohepatic recirculation, but it is quantitatively eliminated over 3 days as a result of selective secretion into bile and selective enrichment within the lumen of the intestine. These findings suggest that cholesterol absorption is structurally specific and likely to be mediated by enantiospecific cellular proteins.

Supplementary key words cholesterol absorption • enantiomer • deuterium • mass spectrometry • animal studies

Abbreviations: NPC1L1, Niemann-Pick C1-Like 1


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