Enhanced hepatic apoA-I secretion and peripheral efflux of cholesterol and phospholipid in CD36 null mice.
CD36 facilitates oxidized low density lipoprotein uptake and is implicated in development of atherosclerotic lesions. CD36 also binds unmodified high and very low density lipoproteins (HDL, VLDL) but its role in the metabolism of these particles is unclear. Several polymorphisms in the CD36 gene wer...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2010-03-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC2845618?pdf=render |
id |
doaj-0aade42afc04473986b942778bd5465b |
---|---|
record_format |
Article |
spelling |
doaj-0aade42afc04473986b942778bd5465b2020-11-24T21:26:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-03-0153e990610.1371/journal.pone.0009906Enhanced hepatic apoA-I secretion and peripheral efflux of cholesterol and phospholipid in CD36 null mice.Pin YueZhouji ChenFatiha NassirCarlos Bernal-MizrachiBrian FinckSalman AzharNada A AbumradCD36 facilitates oxidized low density lipoprotein uptake and is implicated in development of atherosclerotic lesions. CD36 also binds unmodified high and very low density lipoproteins (HDL, VLDL) but its role in the metabolism of these particles is unclear. Several polymorphisms in the CD36 gene were recently shown to associate with serum HDL cholesterol. To gain insight into potential mechanisms for these associations we examined HDL metabolism in CD36 null (CD36(-/-)) mice. Feeding CD36(-/-) mice a high cholesterol diet significantly increased serum HDL, cholesterol and phospholipids, as compared to wild type mice. HDL apolipoproteins apoA-I and apoA-IV were increased and shifted to higher density HDL fractions suggesting altered particle maturation. Clearance of dual-labeled HDL was unchanged in CD36(-/-) mice and cholesterol uptake from HDL or LDL by isolated CD36(-/-) hepatocytes was unaltered. However, CD36(-/-) hepatocytes had higher cholesterol and phospholipid efflux rates. In addition, expression and secretion of apoA-I and apoA-IV were increased reflecting enhanced PXR. Similar to hepatocytes, cholesterol and phospholipid efflux were enhanced in CD36(-/-) macrophages without changes in protein levels of ABCA1, ABCG1 or SR-B1. However, biotinylation assays showed increased surface ABCA1 localization in CD36(-/-) cells. In conclusion, CD36 influences reverse cholesterol transport and hepatic ApoA-I production. Both pathways are enhanced in CD36 deficiency, increasing HDL concentrations, which suggests the potential benefit of CD36 inhibition.http://europepmc.org/articles/PMC2845618?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pin Yue Zhouji Chen Fatiha Nassir Carlos Bernal-Mizrachi Brian Finck Salman Azhar Nada A Abumrad |
spellingShingle |
Pin Yue Zhouji Chen Fatiha Nassir Carlos Bernal-Mizrachi Brian Finck Salman Azhar Nada A Abumrad Enhanced hepatic apoA-I secretion and peripheral efflux of cholesterol and phospholipid in CD36 null mice. PLoS ONE |
author_facet |
Pin Yue Zhouji Chen Fatiha Nassir Carlos Bernal-Mizrachi Brian Finck Salman Azhar Nada A Abumrad |
author_sort |
Pin Yue |
title |
Enhanced hepatic apoA-I secretion and peripheral efflux of cholesterol and phospholipid in CD36 null mice. |
title_short |
Enhanced hepatic apoA-I secretion and peripheral efflux of cholesterol and phospholipid in CD36 null mice. |
title_full |
Enhanced hepatic apoA-I secretion and peripheral efflux of cholesterol and phospholipid in CD36 null mice. |
title_fullStr |
Enhanced hepatic apoA-I secretion and peripheral efflux of cholesterol and phospholipid in CD36 null mice. |
title_full_unstemmed |
Enhanced hepatic apoA-I secretion and peripheral efflux of cholesterol and phospholipid in CD36 null mice. |
title_sort |
enhanced hepatic apoa-i secretion and peripheral efflux of cholesterol and phospholipid in cd36 null mice. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2010-03-01 |
description |
CD36 facilitates oxidized low density lipoprotein uptake and is implicated in development of atherosclerotic lesions. CD36 also binds unmodified high and very low density lipoproteins (HDL, VLDL) but its role in the metabolism of these particles is unclear. Several polymorphisms in the CD36 gene were recently shown to associate with serum HDL cholesterol. To gain insight into potential mechanisms for these associations we examined HDL metabolism in CD36 null (CD36(-/-)) mice. Feeding CD36(-/-) mice a high cholesterol diet significantly increased serum HDL, cholesterol and phospholipids, as compared to wild type mice. HDL apolipoproteins apoA-I and apoA-IV were increased and shifted to higher density HDL fractions suggesting altered particle maturation. Clearance of dual-labeled HDL was unchanged in CD36(-/-) mice and cholesterol uptake from HDL or LDL by isolated CD36(-/-) hepatocytes was unaltered. However, CD36(-/-) hepatocytes had higher cholesterol and phospholipid efflux rates. In addition, expression and secretion of apoA-I and apoA-IV were increased reflecting enhanced PXR. Similar to hepatocytes, cholesterol and phospholipid efflux were enhanced in CD36(-/-) macrophages without changes in protein levels of ABCA1, ABCG1 or SR-B1. However, biotinylation assays showed increased surface ABCA1 localization in CD36(-/-) cells. In conclusion, CD36 influences reverse cholesterol transport and hepatic ApoA-I production. Both pathways are enhanced in CD36 deficiency, increasing HDL concentrations, which suggests the potential benefit of CD36 inhibition. |
url |
http://europepmc.org/articles/PMC2845618?pdf=render |
work_keys_str_mv |
AT pinyue enhancedhepaticapoaisecretionandperipheraleffluxofcholesterolandphospholipidincd36nullmice AT zhoujichen enhancedhepaticapoaisecretionandperipheraleffluxofcholesterolandphospholipidincd36nullmice AT fatihanassir enhancedhepaticapoaisecretionandperipheraleffluxofcholesterolandphospholipidincd36nullmice AT carlosbernalmizrachi enhancedhepaticapoaisecretionandperipheraleffluxofcholesterolandphospholipidincd36nullmice AT brianfinck enhancedhepaticapoaisecretionandperipheraleffluxofcholesterolandphospholipidincd36nullmice AT salmanazhar enhancedhepaticapoaisecretionandperipheraleffluxofcholesterolandphospholipidincd36nullmice AT nadaaabumrad enhancedhepaticapoaisecretionandperipheraleffluxofcholesterolandphospholipidincd36nullmice |
_version_ |
1725979140707844096 |