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 journalArticlepeer-review

97 Scopus citations


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.

Original languageEnglish
Pages (from-to)96-102
Number of pages7
JournalCell Metabolism
Issue number1
StatePublished - 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.



ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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