Submitted on April 11, 2006
Revised on August 25, 2006
Accepted on August 26, 2006
Rapid transient absorption and biliary secretion of enantiomeric cholesterol in hamsters
Emily J. Westover, Xiaobo Lin, Terrence E. Riehl, Lina Ma, William F. Stenson, Douglas F. Covey, and Richard E. Ostlund . Jr
Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO 63110
Corresponding Author: 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 minutes was similar, but cholesterol was temporarily retained there whereas mucosal ent-cholesterol rapidly declined 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/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 is quantitatively eliminated over 3 days due to 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.
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