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Correspondence to:
Attilio Rigotti, To whom correspondence should be addressed., arigotti{at}med.puc.cl (E-mail)
The scavenger receptor class B type I (SR-BI), which is expressed in the liver and intestine, plays a critical role in cholesterol metabolism in rodents. While hepatic SR-BI expression controls high density lipoprotein (HDL) cholesterol metabolism, intestinal SR-BI has been proposed to facilitate cholesterol absorption. To evaluate further the relevance of SR-BI in the enterohepatic circulation of cholesterol and bile salts, we studied biliary lipid secretion, hepatic sterol content and synthesis, bile acid metabolism, fecal neutral sterol excretion, and intestinal cholesterol absorption in SR-BI knockout mice. SR-BI deficiency selectively impaired biliary cholesterol secretion, without concomitant changes in either biliary bile acid or phospholipid secretion. Hepatic total and unesterified cholesterol contents were slightly increased in SR-BI-deficient mice, while sterol synthesis was not significantly changed. Bile acid pool size and composition, as well as fecal bile acid excretion, were not altered in SR-BI knockout mice. Intestinal cholesterol absorption was somewhat increased and fecal sterol excretion was slightly decreased in SR-BI knockout mice relative to controls.
These findings establish the critical role of hepatic SR-BI expression in selectively controlling the utilization of HDL cholesterol for biliary secretion. In contrast, SR-BI expression is not essential for intestinal cholesterol absorption. — Mardones, P., V. Quiñones, L. Amigo, M. Moreno, J. F. Miquel, M. Schwarz, H. E. Miettinen, B. Trigatti, M. Krieger, S. VanPatten, D. E. Cohen, and A. Rigotti. Hepatic cholesterol and bile acid metabolism and intestinal cholesterol absorption in scavenger receptor class B type I-deficient mice. J. Lipid Res. 2001. 42: 170;–180.
Supplementary key words:
HDL, biliary lipids, sterol synthesis, hepatic gene expression, cholesterol feeding
Copyright © 2001 by Lipid Research, Inc.
Original Article
Hepatic cholesterol and bile acid metabolism and intestinal cholesterol absorption in scavenger receptor class B type I-deficient mice
Pablo Mardonesa,
Verónica Quiñonesa,
Ludwig Amigoa,
Mauricio Morenoa,
Juan Francisco Miquela,
Margrit Schwarzb,
Helena E. Miettinenc,
Bernardo Trigattic,
Monty Kriegerc,
Sonya VanPattend,
David E. Cohend, and
Attilio Rigottia
a Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Santiago, Chile
b Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390
c Biology Department, Massachusetts Institute of Technology, Cambridge, MA 02139
d Departments of Medicine and Biochemistry, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461
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