TY - JOUR
T1 - Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice
AU - Bura, Kanwardeep S.
AU - Lord, Caleb
AU - Marshall, Stephanie
AU - McDaniel, Allison
AU - Thomas, Gwyn
AU - Warrier, Manya
AU - Zhang, Jun
AU - Davis, Matthew A.
AU - Sawyer, Janet K.
AU - Shah, Ramesh
AU - Wilson, Martha D.
AU - Dikkers, Arne
AU - Tietge, Uwe J.F.
AU - Collet, Xavier
AU - Rudel, Lawrence L.
AU - Temel, Ryan E.
AU - Brown, J. Mark
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
KW - Fecal neutral sterol excretion
KW - Reverse cholesterol transport
KW - Scavenger receptor class B type I
UR - https://www.scopus.com/pages/publications/84877905245
UR - https://www.scopus.com/pages/publications/84877905245#tab=citedBy
U2 - 10.1194/jlr.M034454
DO - 10.1194/jlr.M034454
M3 - Article
C2 - 23564696
AN - SCOPUS:84877905245
SN - 0022-2275
VL - 54
SP - 1567
EP - 1577
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 6
ER -