Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice

Kanwardeep S. Bura; Caleb Lord; Stephanie Marshall; Allison McDaniel; Gwyn Thomas; Manya Warrier; Jun Zhang; Matthew A. Davis; Janet K. Sawyer; Ramesh Shah; Martha D. Wilson; Arne Dikkers; Uwe J.F. Tietge; Xavier Collet; Lawrence L. Rudel; Ryan E. Temel; J.Mark Brown

Journal of Lipid Research (Jun 2013)

Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice

Kanwardeep S. Bura,
Caleb Lord,
Stephanie Marshall,
Allison McDaniel,
Gwyn Thomas,
Manya Warrier,
Jun Zhang,
Matthew A. Davis,
Janet K. Sawyer,
Ramesh Shah,
Martha D. Wilson,
Arne Dikkers,
Uwe J.F. Tietge,
Xavier Collet,
Lawrence L. Rudel,
Ryan E. Temel,
J.Mark Brown

Affiliations

Kanwardeep S. Bura: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC
Caleb Lord: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC
Stephanie Marshall: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC
Allison McDaniel: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC
Gwyn Thomas: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC
Manya Warrier: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC
Jun Zhang: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC
Matthew A. Davis: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC
Janet K. Sawyer: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC
Ramesh Shah: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC
Martha D. Wilson: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC
Arne Dikkers: Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Uwe J.F. Tietge: Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Xavier Collet: INSERM U1048, Institute of Metabolic and Cardiovascular Diseases of Rangueil Hospital, BP 84225, Toulouse, France
Lawrence L. Rudel: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC
Ryan E. Temel: To whom correspondence should be addressed. Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195. (J.M.B); (R.E.T); Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC; To whom correspondence should be addressed. Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195. (J.M.B); (R.E.T)
J.Mark Brown: To whom correspondence should be addressed. Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195. (J.M.B); (R.E.T); Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC; To whom correspondence should be addressed. Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195. (J.M.B); (R.E.T)

Journal volume & issue: Vol. 54, no. 6
pp. 1567 – 1577

Abstract

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Reverse cholesterol transport (RCT) can proceed through the classic hepatobiliary route or through the nonbiliary transintestinal cholesterol efflux (TICE) pathway. Scavenger receptor class B type I (SR-BI) plays a critical role in the classic hepatobiliary route of RCT. However, the role of SR-BI in TICE has not been studied. To examine the role of intestinal SR-BI in TICE, sterol balance was measured in control mice and mice transgenically overexpressing SR-BI in the proximal small intestine (SR-BIhApoCIII-ApoAIV-Tg). SR-BIhApoCIII-ApoAIV-Tg mice had significantly lower plasma cholesterol levels compared with wild-type controls, yet SR-BIhApoCIII-ApoAIV-Tg mice had normal fractional cholesterol absorption and fecal neutral sterol excretion. Both in the absence or presence of ezetimibe, intestinal SR-BI overexpression had no impact on the amount of cholesterol excreted in the feces. To specifically study effects of intestinal SR-BI on TICE we crossed SR-BIhApoCIII-ApoAIV-Tg mice into a mouse model that preferentially utilized the TICE pathway for RCT (Niemann-Pick C1-like 1 liver transgenic), and likewise found no alterations in cholesterol absorption or fecal sterol excretion. Finally, mice lacking SR-BI in all tissues also exhibited normal cholesterol absorption and fecal cholesterol disposal. Collectively, these results suggest that SR-BI is not rate limiting for intestinal cholesterol absorption or for fecal neutral sterol loss through the TICE pathway.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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