title: Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice.
abstract: 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-BI(hApoCIII-ApoAIV-Tg)). SR-BI(hApoCIII-ApoAIV-Tg) mice had significantly lower plasma cholesterol levels compared with wild-type controls, yet SR-BI(hApoCIII-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-BI(hApoCIII-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.
authors.affiliation: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Kanwardeep S
authors.initials: KS
authors.lastname: Bura
authors.affiliation: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Caleb
authors.initials: C
authors.lastname: Lord
authors.affiliation: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Marshall
authors.affiliation: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Allison
authors.initials: A
authors.lastname: McDaniel
authors.affiliation: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Gwyn
authors.initials: G
authors.lastname: Thomas
authors.affiliation: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Manya
authors.initials: M
authors.lastname: Warrier
authors.affiliation: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Davis
authors.affiliation: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Janet K
authors.initials: JK
authors.lastname: Sawyer
authors.affiliation: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Shah
authors.affiliation: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Martha D
authors.initials: MD
authors.lastname: Wilson
authors.affiliation: Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Arne
authors.initials: A
authors.lastname: Dikkers
authors.affiliation: Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Uwe J F
authors.initials: UJF
authors.lastname: Tietge
authors.affiliation: INSERM U1048, Institute of Metabolic and Cardiovascular Diseases of Rangueil Hospital, BP 84225, Toulouse, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Collet
authors.affiliation: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Rudel
authors.affiliation: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC. Electronic address: rtemel@wakehealth.edu.
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Temel
authors.affiliation: Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC. Electronic address: brownm5@ccf.org.
authors.forename: J Mark
authors.initials: JM
authors.lastname: Brown
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001384:Azetidines / Q000494:pharmacology; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D000069438:Ezetimibe; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol; D000069438:Ezetimibe
keywords: fecal neutral sterol excretion; reverse cholesterol transport; scavenger receptor class B type I
references.citation: Biochim Biophys Acta. 2007 Sep;1771(9):1132-9
references.pmid: 17442616
references.citation: J Biol Chem. 1993 Sep 5;268(25):18929-35
references.pmid: 7689561
references.citation: J Lipid Res. 2001 Jun;42(6):902-9
references.pmid: 11369797
references.citation: J Biol Chem. 1998 Dec 4;273(49):32920-6
references.pmid: 9830042
references.citation: Nat Med. 2001 Jul;7(7):853-7
references.pmid: 11433352
references.citation: J Biol Chem. 2001 Jul 6;276(27):25287-93
references.pmid: 11301333
references.citation: J Lipid Res. 2009 Jul;50(7):1316-29
references.pmid: 19286647
references.citation: J Biol Chem. 1999 Jan 22;274(4):2366-71
references.pmid: 9891004
references.citation: Arterioscler Thromb Vasc Biol. 2011 Aug;31(8):1726-33
references.pmid: 21571685
references.citation: Circulation. 2002 Dec 17;106(25):3143-421
references.pmid: 12485966
references.citation: Gastroenterology. 2007 Sep;133(3):967-75
references.pmid: 17854600
references.citation: J Lipid Res. 2009 Aug;50(8):1571-80
references.pmid: 19252221
references.citation: Circulation. 2005 Jun 28;111(25):3457-64
references.pmid: 15967843
references.citation: Arterioscler Thromb Vasc Biol. 2000 Mar;20(3):721-7
references.pmid: 10712397
references.citation: Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):139-43
references.pmid: 19797709
references.citation: J Lipid Res. 2005 Nov;46(11):2423-31
references.pmid: 16150828
references.citation: J Clin Invest. 2007 Jul;117(7):1968-78
references.pmid: 17571164
references.citation: Annu Rev Nutr. 1992;12:299-326
references.pmid: 1503808
references.citation: Am J Med. 1977 May;62(5):707-14
references.pmid: 193398
references.citation: J Clin Invest. 1996 Aug 15;98(4):984-95
references.pmid: 8770871
references.citation: Circulation. 2012 Jan 3;125(1):e2-e220
references.pmid: 22179539
references.citation: Hepatology. 2009 Oct;50(4):1263-72
references.pmid: 19637290
references.citation: J Lipid Res. 2004 Mar;45(3):427-37
references.pmid: 14679167
references.citation: J Lipid Res. 2009 Oct;50(10):2046-54
references.pmid: 19439761
references.citation: Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16237-42
references.pmid: 12444248
references.citation: Gastroenterology. 2008 Jun;134(7):2091-100
references.pmid: 18466903
references.citation: J Lipid Res. 2001 Feb;42(2):170-80
references.pmid: 11181745
references.citation: Gastroenterology. 2005 Jan;128(1):147-56
references.pmid: 15633131
references.citation: PLoS One. 2009;4(1):e4278
references.pmid: 19169357
references.citation: Gastroenterology. 2011 Mar;140(3):1043-51
references.pmid: 21134376
references.citation: J Biol Chem. 1994 Aug 19;269(33):21003-9
references.pmid: 7520436
references.citation: Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12610-5
references.pmid: 9356497
references.citation: J Biol Chem. 2009 Jul 17;284(29):19211-9
references.pmid: 19416968
references.citation: J Biol Chem. 1999 Mar 12;274(11):7165-71
references.pmid: 10066776
references.citation: Biochemistry. 1998 Dec 22;37(51):17843-50
references.pmid: 9922151
references.citation: Curr Opin Lipidol. 2012 Apr;23(2):85-90
references.pmid: 22262055
references.citation: Circulation. 2008 Sep 30;118(14):1467-75
references.pmid: 18794388
references.citation: J Biol Chem. 2007 Jan 12;282(2):1445-55
references.pmid: 17105723
references.citation: J Biol Chem. 2006 Mar 17;281(11):7214-9
references.pmid: 16421100
references.citation: Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9322-7
references.pmid: 10430941
references.citation: Circ Res. 2004 Oct 15;95(8):764-72
references.pmid: 15486323
references.citation: Circulation. 2012 Apr 17;125(15):1905-19
references.pmid: 22508840
references.citation: J Lipid Res. 2009 Nov;50(11):2235-44
references.pmid: 19454765
references.citation: Curr Opin Cardiol. 2007 Jul;22(4):368-72
references.pmid: 17556891
references.citation: J Biol Chem. 2002 Sep 13;277(37):34125-35
references.pmid: 12110672
references.citation: Circ Res. 2002 Feb 22;90(3):270-6
references.pmid: 11861414
references.citation: J Biol Chem. 2008 Apr 18;283(16):10522-34
references.pmid: 18281279
references.citation: Science. 1996 Jan 26;271(5248):518-20
references.pmid: 8560269
references.citation: Cell Metab. 2010 Jul 7;12(1):96-102
references.pmid: 20620999
references.citation: Am J Physiol Gastrointest Liver Physiol. 2008 Jul;295(1):G203-G208
references.pmid: 18511744
references.citation: Am J Pathol. 1994 Nov;145(5):1237-45
references.pmid: 7977654
references.citation: Nutr Metab (Lond). 2012 Mar 29;9(1):25
references.pmid: 22458435
references.citation: Circ Res. 2013 Jan 4;112(1):140-51
references.pmid: 23023567
references.citation: J Clin Invest. 2005 Oct;115(10):2870-4
references.pmid: 16200214
references.citation: J Biol Chem. 1999 Nov 19;274(47):33398-402
references.pmid: 10559220
references.citation: Nature. 1997 May 22;387(6631):414-7
references.pmid: 9163428
references.citation: Clin Biochem. 1993 Feb;26(1):39-42
references.pmid: 8448837
references.citation: J Clin Invest. 1995 Mar;95(3):1124-32
references.pmid: 7883961
references.citation: J Biol Chem. 2000 Jul 7;275(27):20368-73
references.pmid: 10751392
references.citation: Am J Physiol Gastrointest Liver Physiol. 2011 Aug;301(2):G326-37
references.pmid: 21546579
references.citation: Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6731-5
references.pmid: 1907375
references.citation: Gastroenterol Clin North Am. 1991 Mar;20(1):21-46
references.pmid: 2022424
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3845-50
references.pmid: 15007173
references.citation: J Clin Invest. 2001 Sep;108(6):843-50
references.pmid: 11560953
references.citation: J Biol Chem. 2002 Feb 8;277(6):3801-4
references.pmid: 11733542
references.citation: Biochim Biophys Acta. 2002 Jan 30;1580(1):77-93
references.pmid: 11923102
references.citation: Science. 2009 Jul 3;325(5936):100-4
references.pmid: 19520913
references.citation: Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4619-24
references.pmid: 9539787
references.citation: J Lipid Res. 2012 Oct;53(10):2017-2023
references.pmid: 22802462
references.citation: Curr Opin Lipidol. 1997 Jun;8(3):181-8
references.pmid: 9211067
references.citation: J Lipid Res. 1978 Sep;19(7):924-8
references.pmid: 712252
references.citation: J Lipid Res. 2003 Sep;44(9):1605-13
references.pmid: 12810817
references.citation: J Lipid Res. 1998 Nov;39(11):2143-9
references.pmid: 9799800