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 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.
Temel
Ryan E
RE
Section on Lipid Sciences, Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
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
D000818:Animals; D001659:Biliary Tract / Q000378:metabolism*; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D013261:Sterols / Q000378:metabolism*
D026901:Membrane Transport Proteins; C482445:Npc1l1 protein, mouse; D013261:Sterols; D002784:Cholesterol