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Biliary sterol secretion is not required for macrophage reverse cholesterol transport.


ABSTRACT: Recent evidence suggests that the intestine may play a direct facilitative role in reverse cholesterol transport (RCT), independent of hepatobiliary secretion. In order to understand the nonbiliary pathway for RCT, we created both genetic and surgical models of biliary cholesterol insufficiency. To genetically inhibit biliary cholesterol secretion, we generated mice in which Niemann-Pick C1-Like 1 (NPC1L1) was overexpressed in the liver. Compared to controls, NPC1L1(Liver-Tg) mice exhibit a >90% decrease in biliary cholesterol secretion, yet mass fecal sterol loss and macrophage RCT are normal. To surgically inhibit biliary emptying into the intestine, we have established an acute biliary diversion model. Strikingly, macrophage RCT persists in mice surgically lacking the ability to secrete bile into the intestine. Collectively, these studies demonstrate that mass fecal sterol loss and macrophage RCT can proceed in the absence of biliary sterol secretion, challenging the obligate role of bile in RCT.

SUBMITTER: Temel RE 

PROVIDER: S-EPMC2913877 | biostudies-other | 2010 Jul

REPOSITORIES: biostudies-other

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Biliary sterol secretion is not required for macrophage reverse cholesterol transport.

Temel Ryan E RE   Sawyer Janet K JK   Yu Liqing L   Lord Caleb C   Degirolamo Chiara C   McDaniel Allison A   Marshall Stephanie S   Wang Nanping N   Shah Ramesh R   Rudel Lawrence L LL   Brown J Mark JM  

Cell metabolism 20100701 1


Recent evidence suggests that the intestine may play a direct facilitative role in reverse cholesterol transport (RCT), independent of hepatobiliary secretion. In order to understand the nonbiliary pathway for RCT, we created both genetic and surgical models of biliary cholesterol insufficiency. To genetically inhibit biliary cholesterol secretion, we generated mice in which Niemann-Pick C1-Like 1 (NPC1L1) was overexpressed in the liver. Compared to controls, NPC1L1(Liver-Tg) mice exhibit a >90%  ...[more]

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