ABCA1-dependent lipid efflux to apolipoprotein A-I mediates HDL particle formation and decreases VLDL secretion from murine hepatocytes
High levels of expression of the ATP binding cassette transporter A1 (ABCA1) in the liver and the need to over- or underexpress hepatic ABCA1 to impact plasma HDL levels in mice suggest a major role of the liver in HDL formation and in determining circulating HDL levels. Cultured murine hepatocytes...
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| Format: | Article |
| Language: | English |
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Elsevier
2004-06-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520318101 |
| _version_ | 1818384603020263424 |
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| author | Daisy Sahoo Timothy C. Trischuk Teddy Chan Victor A.B. Drover Samuel Ho Giovanna Chimini Luis B. Agellon Ricky Agnihotri Gordon A. Francis Richard Lehner |
| author_facet | Daisy Sahoo Timothy C. Trischuk Teddy Chan Victor A.B. Drover Samuel Ho Giovanna Chimini Luis B. Agellon Ricky Agnihotri Gordon A. Francis Richard Lehner |
| author_sort | Daisy Sahoo |
| collection | DOAJ |
| description | High levels of expression of the ATP binding cassette transporter A1 (ABCA1) in the liver and the need to over- or underexpress hepatic ABCA1 to impact plasma HDL levels in mice suggest a major role of the liver in HDL formation and in determining circulating HDL levels. Cultured murine hepatocytes were used to examine the role of hepatic ABCA1 in mediating the lipidation of apolipoprotein A-I (apoA-I) for HDL particle formation. Exogenous apoA-I stimulated cholesterol efflux to the medium from wild-type hepatocytes, but not from ABCA1-deficient (abca1−/−) hepatocytes. ApoA-I induced the formation of new HDL particles and enhanced the lipidation of endogenously secreted murine apoA-I in ABCA1-expressing but not abca1−/− hepatocytes. ABCA1-dependent cholesterol mobilization to apoA-I increased new cholesterol synthesis, indicating depletion of the regulatory pool of hepatocyte cholesterol during HDL formation. Secretion of triacylglycerol and apoB was decreased following apoA-I incubation with ABCA1-expressing but not abca1−/− hepatocytes.These results support a major role for hepatocyte ABCA1 in generating a critical pool of HDL precursor particles that enhance further HDL generation and passive cholesterol mobilization in the periphery. The results also suggest that diversion of hepatocyte cholesterol into the “reverse” cholesterol transport pathway diminishes cholesterol availability for apoB-containing lipoprotein secretion by the liver. |
| first_indexed | 2024-12-14T03:24:53Z |
| format | Article |
| id | doaj.art-518a688a2884449ab0e0a8945b3d8d8a |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T03:24:53Z |
| publishDate | 2004-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-518a688a2884449ab0e0a8945b3d8d8a2022-12-21T23:18:54ZengElsevierJournal of Lipid Research0022-22752004-06-0145611221131ABCA1-dependent lipid efflux to apolipoprotein A-I mediates HDL particle formation and decreases VLDL secretion from murine hepatocytesDaisy Sahoo0Timothy C. Trischuk1Teddy Chan2Victor A.B. Drover3Samuel Ho4Giovanna Chimini5Luis B. Agellon6Ricky Agnihotri7Gordon A. Francis8Richard Lehner9Department of Pediatrics, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Biochemistry, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Cell Biology, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Centre d'Immunologie, INSERM-CNRS de Marseille Luminy, Marseille, FranceDepartment of Pediatrics, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Biochemistry, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Cell Biology, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Centre d'Immunologie, INSERM-CNRS de Marseille Luminy, Marseille, FranceDepartment of Pediatrics, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Biochemistry, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Cell Biology, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Centre d'Immunologie, INSERM-CNRS de Marseille Luminy, Marseille, FranceDepartment of Pediatrics, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Biochemistry, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Cell Biology, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Centre d'Immunologie, INSERM-CNRS de Marseille Luminy, Marseille, FranceDepartment of Pediatrics, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Biochemistry, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Cell Biology, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Centre d'Immunologie, INSERM-CNRS de Marseille Luminy, Marseille, FranceDepartment of Pediatrics, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Biochemistry, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Cell Biology, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Centre d'Immunologie, INSERM-CNRS de Marseille Luminy, Marseille, FranceDepartment of Pediatrics, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Biochemistry, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Cell Biology, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Centre d'Immunologie, INSERM-CNRS de Marseille Luminy, Marseille, FranceDepartment of Pediatrics, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Biochemistry, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Cell Biology, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Centre d'Immunologie, INSERM-CNRS de Marseille Luminy, Marseille, FranceDepartment of Pediatrics, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Biochemistry, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Cell Biology, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Centre d'Immunologie, INSERM-CNRS de Marseille Luminy, Marseille, FranceDepartment of Pediatrics, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Biochemistry, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Department of Cell Biology, CIHR Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada; Centre d'Immunologie, INSERM-CNRS de Marseille Luminy, Marseille, FranceHigh levels of expression of the ATP binding cassette transporter A1 (ABCA1) in the liver and the need to over- or underexpress hepatic ABCA1 to impact plasma HDL levels in mice suggest a major role of the liver in HDL formation and in determining circulating HDL levels. Cultured murine hepatocytes were used to examine the role of hepatic ABCA1 in mediating the lipidation of apolipoprotein A-I (apoA-I) for HDL particle formation. Exogenous apoA-I stimulated cholesterol efflux to the medium from wild-type hepatocytes, but not from ABCA1-deficient (abca1−/−) hepatocytes. ApoA-I induced the formation of new HDL particles and enhanced the lipidation of endogenously secreted murine apoA-I in ABCA1-expressing but not abca1−/− hepatocytes. ABCA1-dependent cholesterol mobilization to apoA-I increased new cholesterol synthesis, indicating depletion of the regulatory pool of hepatocyte cholesterol during HDL formation. Secretion of triacylglycerol and apoB was decreased following apoA-I incubation with ABCA1-expressing but not abca1−/− hepatocytes.These results support a major role for hepatocyte ABCA1 in generating a critical pool of HDL precursor particles that enhance further HDL generation and passive cholesterol mobilization in the periphery. The results also suggest that diversion of hepatocyte cholesterol into the “reverse” cholesterol transport pathway diminishes cholesterol availability for apoB-containing lipoprotein secretion by the liver.http://www.sciencedirect.com/science/article/pii/S0022227520318101ATP binding cassette transporter A1atherosclerosischolesteroleffluxtriacylglyceroltriglyceride |
| spellingShingle | Daisy Sahoo Timothy C. Trischuk Teddy Chan Victor A.B. Drover Samuel Ho Giovanna Chimini Luis B. Agellon Ricky Agnihotri Gordon A. Francis Richard Lehner ABCA1-dependent lipid efflux to apolipoprotein A-I mediates HDL particle formation and decreases VLDL secretion from murine hepatocytes Journal of Lipid Research ATP binding cassette transporter A1 atherosclerosis cholesterol efflux triacylglycerol triglyceride |
| title | ABCA1-dependent lipid efflux to apolipoprotein A-I mediates HDL particle formation and decreases VLDL secretion from murine hepatocytes |
| title_full | ABCA1-dependent lipid efflux to apolipoprotein A-I mediates HDL particle formation and decreases VLDL secretion from murine hepatocytes |
| title_fullStr | ABCA1-dependent lipid efflux to apolipoprotein A-I mediates HDL particle formation and decreases VLDL secretion from murine hepatocytes |
| title_full_unstemmed | ABCA1-dependent lipid efflux to apolipoprotein A-I mediates HDL particle formation and decreases VLDL secretion from murine hepatocytes |
| title_short | ABCA1-dependent lipid efflux to apolipoprotein A-I mediates HDL particle formation and decreases VLDL secretion from murine hepatocytes |
| title_sort | abca1 dependent lipid efflux to apolipoprotein a i mediates hdl particle formation and decreases vldl secretion from murine hepatocytes |
| topic | ATP binding cassette transporter A1 atherosclerosis cholesterol efflux triacylglycerol triglyceride |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520318101 |
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