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

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Reverse cholesterol transport (RCT) can proceed through the classic hepatobiliary route or through the non-biliary 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-BI hApoCIII-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.

Original languageEnglish
Pages (from-to)1567-1577
Number of pages11
JournalJournal of Lipid Research
Volume54
Issue number6
DOIs
StatePublished - Jun 2013

Keywords

  • Fecal neutral sterol excretion
  • Reverse cholesterol transport
  • Scavenger receptor class B type I

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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