Trans-intestinal cholesterol efflux is not mediated through high density lipoprotein.
Transintestinal cholesterol efflux (TICE) provides an attractive target to increase body cholesterol excretion. At present, the cholesterol donor responsible for direct delivery of plasma cholesterol to the intestine is unknown. In this study, we investigated the role of HDL in TICE. ATP-binding cassette protein A1 deficient (Abca1(-/-)) mice that lack HDL and wild-type (WT) mice were intravenously injected with chylomicron-like emulsion particles that contained radiolabeled cholesterol that is liberated in the liver and partly reenters the circulation. Both groups secreted radiolabeled cholesterol from plasma into intestinal lumen and TICE was unaltered between the two mouse models. To further investigate the role of HDL, we injected HDL with radiolabeled cholesterol in WT mice and Abca1(-/-)×Sr-b1(-/-) mice that lack HDL and are also unable to clear HDL via the liver. The intestines of both mice were unable to take up and secrete radiolabeled cholesterol from HDL via TICE. Although a generally accepted major player in the hepatobiliary route-based cholesterol excretion, HDL plays no significant role in TICE in mice.
Department of Medical Biochemistry, Amsterdam, The Netherlands; AMC Tytgat Institute, Academic Medical Center, Amsterdam, The Netherlands.
Carlos L J
CLJ
Vrins
Department of Medical Biochemistry, Amsterdam, The Netherlands.
Roelof
R
Ottenhoff
AMC Tytgat Institute, Academic Medical Center, Amsterdam, The Netherlands.
Karin
K
van den Oever
AMC Tytgat Institute, Academic Medical Center, Amsterdam, The Netherlands.
Dirk R
DR
de Waart
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
J Kar
JK
Kruyt
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
Ying
Y
Zhao
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
Theo J C
TJC
van Berkel
Department of General Internal Medicine, Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; and.
Louis M
LM
Havekes
Department of Medical Biochemistry, Amsterdam, The Netherlands.
Johannes M
JM
Aerts
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
Miranda
M
van Eck
Department of General Internal Medicine, Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; and.
Patrick C N
PCN
Rensen
Department of Pediatrics/Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: A.K.Groen@umcg.nl.
Albert K
AK
Groen
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008075:Lipoproteins, HDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol