Biliary sterol secretion is not required for macrophage reverse cholesterol transport

Ryan E. Temel; Janet K. Sawyer; Liqing Yu; Caleb Lord; Chiara Degirolamo; Allison McDaniel; Stephanie Marshall; Nanping Wang; Ramesh Shah; Lawrence L. Rudel; J. Mark Brown

doi:10.1016/j.cmet.2010.05.011

Biliary sterol secretion is not required for macrophage reverse cholesterol transport

Ryan E. Temel, Janet K. Sawyer, Liqing Yu, Caleb Lord, Chiara Degirolamo, Allison McDaniel, Stephanie Marshall, Nanping Wang, Ramesh Shah, Lawrence L. Rudel, J. Mark Brown

Research output: Contribution to journal › Article › peer-review

99 Scopus citations

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.

Original language	English
Pages (from-to)	96-102
Number of pages	7
Journal	Cell Metabolism
Volume	12
Issue number	1
DOIs	https://doi.org/10.1016/j.cmet.2010.05.011
State	Published - Jul 7 2010

Bibliographical note

Funding Information:
We sincerely thank Paul Dawson (Wake Forest University) for critical reading of this manuscript and providing meaningful input into these studies. We also thank George Rothblat (The Children's Hospital of Philadelphia) for providing J774 macrophages. This work was supported by the National Heart, Lung, and Blood Institute through a pathway to independence grant (1K99-HL096166 to J.M.B.) and a program project grant (5P01HL049373 to L.L.R.). L.Y. is supported by a Scientist Development Grant (#0635261N) from the American Heart Association. L.L.R. is a member of the Merck speaker's bureau.

Keywords

HUMDISEASE

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2010.05.011

Cite this

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title = "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, NPC1L1Liver-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.",

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note = "Funding Information: We sincerely thank Paul Dawson (Wake Forest University) for critical reading of this manuscript and providing meaningful input into these studies. We also thank George Rothblat (The Children's Hospital of Philadelphia) for providing J774 macrophages. This work was supported by the National Heart, Lung, and Blood Institute through a pathway to independence grant (1K99-HL096166 to J.M.B.) and a program project grant (5P01HL049373 to L.L.R.). L.Y. is supported by a Scientist Development Grant (#0635261N) from the American Heart Association. L.L.R. is a member of the Merck speaker's bureau. ",

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AU - McDaniel, Allison

AU - Marshall, Stephanie

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AU - Rudel, Lawrence L.

AU - Brown, J. Mark

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N2 - 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, NPC1L1Liver-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.

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Biliary sterol secretion is not required for macrophage reverse cholesterol transport

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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