Biliary Sterol Secretion Is Not Required for Macrophage Reverse Cholesterol Transport

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...

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Bibliographic Details
Published in:Cell metabolism 2010-07, Vol.12 (1), p.96-102
Main Authors: Temel, Ryan E., Sawyer, Janet K., Yu, Liqing, Lord, Caleb, Degirolamo, Chiara, McDaniel, Allison, Marshall, Stephanie, Wang, Nanping, Shah, Ramesh, Rudel, Lawrence L., Brown, J. Mark
Format: Article
Language:English
Subjects:
Animals
Biliary Tract - metabolism
Biological Transport
Cholesterol - metabolism
HUMDISEASE
Liver - metabolism
Macrophages - immunology
Macrophages - metabolism
Membrane Transport Proteins - genetics
Membrane Transport Proteins - metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Models, Animal
Sterols - metabolism
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Summary: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. ► Mice lacking biliary sterols have normal reverse cholesterol transport (RCT) ► Mice surgically lacking biliary contributions to the intestine have normal RCT ► The conceptual framework of macrophage RCT requires significant modification
ISSN:1550-4131
1932-7420
DOI:10.1016/j.cmet.2010.05.011