Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice.
An effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3880293?pdf=render |
| _version_ | 1818893359013429248 |
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| author | Stephanie M Marshall Kathryn L Kelley Matthew A Davis Martha D Wilson Allison L McDaniel Richard G Lee Rosanne M Crooke Mark J Graham Lawrence L Rudel J Mark Brown Ryan E Temel |
| author_facet | Stephanie M Marshall Kathryn L Kelley Matthew A Davis Martha D Wilson Allison L McDaniel Richard G Lee Rosanne M Crooke Mark J Graham Lawrence L Rudel J Mark Brown Ryan E Temel |
| author_sort | Stephanie M Marshall |
| collection | DOAJ |
| description | An effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways. However, the lipoprotein that moves cholesterol through the plasma to the small intestine for transintestinal cholesterol efflux (TICE) is unknown. To test the hypothesis that hepatic very low-density lipoproteins (VLDL) support TICE, antisense oligonucleotides (ASO) were used to knockdown hepatic expression of microsomal triglyceride transfer protein (MTP), which is necessary for VLDL assembly. While maintained on a high cholesterol diet, Niemann-Pick C1-like 1 hepatic transgenic (L1Tg) mice, which predominantly excrete cholesterol via TICE, and wild type (WT) littermates were treated with control ASO or MTP ASO. In both WT and L1Tg mice, MTP ASO decreased VLDL triglyceride (TG) and cholesterol secretion. Regardless of treatment, L1Tg mice had reduced biliary cholesterol compared to WT mice. However, only L1Tg mice treated with MTP ASO had reduced fecal cholesterol excretion. Based upon these findings, we conclude that VLDL or a byproduct such as LDL can move cholesterol from the liver to the small intestine for TICE. |
| first_indexed | 2024-12-19T18:11:20Z |
| format | Article |
| id | doaj.art-1257b92d3ba44f13a41a71e33d050372 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T18:11:20Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1257b92d3ba44f13a41a71e33d0503722022-12-21T20:11:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8441810.1371/journal.pone.0084418Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice.Stephanie M MarshallKathryn L KelleyMatthew A DavisMartha D WilsonAllison L McDanielRichard G LeeRosanne M CrookeMark J GrahamLawrence L RudelJ Mark BrownRyan E TemelAn effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways. However, the lipoprotein that moves cholesterol through the plasma to the small intestine for transintestinal cholesterol efflux (TICE) is unknown. To test the hypothesis that hepatic very low-density lipoproteins (VLDL) support TICE, antisense oligonucleotides (ASO) were used to knockdown hepatic expression of microsomal triglyceride transfer protein (MTP), which is necessary for VLDL assembly. While maintained on a high cholesterol diet, Niemann-Pick C1-like 1 hepatic transgenic (L1Tg) mice, which predominantly excrete cholesterol via TICE, and wild type (WT) littermates were treated with control ASO or MTP ASO. In both WT and L1Tg mice, MTP ASO decreased VLDL triglyceride (TG) and cholesterol secretion. Regardless of treatment, L1Tg mice had reduced biliary cholesterol compared to WT mice. However, only L1Tg mice treated with MTP ASO had reduced fecal cholesterol excretion. Based upon these findings, we conclude that VLDL or a byproduct such as LDL can move cholesterol from the liver to the small intestine for TICE.http://europepmc.org/articles/PMC3880293?pdf=render |
| spellingShingle | Stephanie M Marshall Kathryn L Kelley Matthew A Davis Martha D Wilson Allison L McDaniel Richard G Lee Rosanne M Crooke Mark J Graham Lawrence L Rudel J Mark Brown Ryan E Temel Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice. PLoS ONE |
| title | Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice. |
| title_full | Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice. |
| title_fullStr | Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice. |
| title_full_unstemmed | Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice. |
| title_short | Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice. |
| title_sort | reduction of vldl secretion decreases cholesterol excretion in niemann pick c1 like 1 hepatic transgenic mice |
| url | http://europepmc.org/articles/PMC3880293?pdf=render |
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