Phospholipid transfer protein gene knock-out mice have low high density lipoprotein levels, due to hypercatabolism, and accumulate apoA-IV-rich lamellar lipoproteins
Phospholipid transfer protein gene knock-out (Pltp KO) mice have defective transfer of very low density lipoprotein (VLDL) phospholipids into high density lipoprotein (HDL) and markedly decreased HDL levels (Jiang et al. 1999. J. Clin. Invest. 103: 907–914). These animals also accumulated VLDL- and...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2000-02-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520320617 |
| _version_ | 1818920522440769536 |
|---|---|
| author | Shucun Qin Koichi Kawano Can Bruce Min Lin Charles Bisgaier Alan R. Tall Xian-cheng Jiang |
| author_facet | Shucun Qin Koichi Kawano Can Bruce Min Lin Charles Bisgaier Alan R. Tall Xian-cheng Jiang |
| author_sort | Shucun Qin |
| collection | DOAJ |
| description | Phospholipid transfer protein gene knock-out (Pltp KO) mice have defective transfer of very low density lipoprotein (VLDL) phospholipids into high density lipoprotein (HDL) and markedly decreased HDL levels (Jiang et al. 1999. J. Clin. Invest. 103: 907–914). These animals also accumulated VLDL- and LDL-sized lipoproteins on a high saturated fat diet. The goals of this study were to further characterize the abnormal lipoproteins of Pltp KO mice and to determine the mechanisms responsible for low HDL levels. A lipoprotein fraction enriched in lamellar structures was isolated from the low density lipoprotein (LDL) region and was shown to be phospholipid- and free cholesterol-rich and to have apoA-IV (55%) and apoE (25%) as major apolipoproteins. The lamellar lipoproteins accumulating in these mice probably represent surface material derived from triglyceride-rich lipoproteins (TRL). The HDL was found to be protein-rich (primarily apoA-I) and specifically depleted in phosphatidylcholine (PC) (28% in wild-type mice (WT) vs. 15% in Pltp KO mice, P < 0.001). Unexpectedly, turnover studies using autologous HDL revealed a profound 4-fold increase in the catabolism of HDL protein and cholesteryl ester in Pltp KO mice compared to wild-type, with minor differences in synthesis rates. In contrast, injection of WT mouse HDL into Pltp KO mice showed only a 2-fold increase in fractional catabolism. Reminiscent of the defect in Tangier disease, the failure of transfer of PC from TRL into the HDL fraction results in dramatic hypercatabolism of HDL. These results suggest that defective phospholipid transfer from TRL into HDL, arising from decreased lipolysis or decreased PLTP activity, could lead to hypoalphalipoproteinemia characterized by hypercatabolism of HDL protein. —Qin, S., K. Kawano, C. Bruce, M. Lin, C. Bisgaier, A. R. Tall, and X-c. Jiang. Phospholipid transfer protein gene knock-out mice have low high density lipoprotein levels, due to hypercatabolism, and accumulate apoA-IV-rich lamellar lipoproteins. |
| first_indexed | 2024-12-20T01:23:05Z |
| format | Article |
| id | doaj.art-4a565001cd124579aca542b316e26698 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T01:23:05Z |
| publishDate | 2000-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-4a565001cd124579aca542b316e266982022-12-21T19:58:21ZengElsevierJournal of Lipid Research0022-22752000-02-01412269276Phospholipid transfer protein gene knock-out mice have low high density lipoprotein levels, due to hypercatabolism, and accumulate apoA-IV-rich lamellar lipoproteinsShucun Qin0Koichi Kawano1Can Bruce2Min Lin3Charles Bisgaier4Alan R. Tall5Xian-cheng Jiang6Division of Molecular Medicine, Department of Medicine, Columbia University, New York NY 10032Division of Molecular Medicine, Department of Medicine, Columbia University, New York NY 10032Division of Molecular Medicine, Department of Medicine, Columbia University, New York NY 10032Division of Molecular Medicine, Department of Medicine, Columbia University, New York NY 10032Esperion Therapeutics, Inc., Ann Arbor, MI 48108Division of Molecular Medicine, Department of Medicine, Columbia University, New York NY 10032To whom correspondence should be addressed.; Division of Molecular Medicine, Department of Medicine, Columbia University, New York NY 10032Phospholipid transfer protein gene knock-out (Pltp KO) mice have defective transfer of very low density lipoprotein (VLDL) phospholipids into high density lipoprotein (HDL) and markedly decreased HDL levels (Jiang et al. 1999. J. Clin. Invest. 103: 907–914). These animals also accumulated VLDL- and LDL-sized lipoproteins on a high saturated fat diet. The goals of this study were to further characterize the abnormal lipoproteins of Pltp KO mice and to determine the mechanisms responsible for low HDL levels. A lipoprotein fraction enriched in lamellar structures was isolated from the low density lipoprotein (LDL) region and was shown to be phospholipid- and free cholesterol-rich and to have apoA-IV (55%) and apoE (25%) as major apolipoproteins. The lamellar lipoproteins accumulating in these mice probably represent surface material derived from triglyceride-rich lipoproteins (TRL). The HDL was found to be protein-rich (primarily apoA-I) and specifically depleted in phosphatidylcholine (PC) (28% in wild-type mice (WT) vs. 15% in Pltp KO mice, P < 0.001). Unexpectedly, turnover studies using autologous HDL revealed a profound 4-fold increase in the catabolism of HDL protein and cholesteryl ester in Pltp KO mice compared to wild-type, with minor differences in synthesis rates. In contrast, injection of WT mouse HDL into Pltp KO mice showed only a 2-fold increase in fractional catabolism. Reminiscent of the defect in Tangier disease, the failure of transfer of PC from TRL into the HDL fraction results in dramatic hypercatabolism of HDL. These results suggest that defective phospholipid transfer from TRL into HDL, arising from decreased lipolysis or decreased PLTP activity, could lead to hypoalphalipoproteinemia characterized by hypercatabolism of HDL protein. —Qin, S., K. Kawano, C. Bruce, M. Lin, C. Bisgaier, A. R. Tall, and X-c. Jiang. Phospholipid transfer protein gene knock-out mice have low high density lipoprotein levels, due to hypercatabolism, and accumulate apoA-IV-rich lamellar lipoproteins.http://www.sciencedirect.com/science/article/pii/S0022227520320617HDLlipoproteinsapolipoproteinsphospholipidsfractional catabolic rate |
| spellingShingle | Shucun Qin Koichi Kawano Can Bruce Min Lin Charles Bisgaier Alan R. Tall Xian-cheng Jiang Phospholipid transfer protein gene knock-out mice have low high density lipoprotein levels, due to hypercatabolism, and accumulate apoA-IV-rich lamellar lipoproteins Journal of Lipid Research HDL lipoproteins apolipoproteins phospholipids fractional catabolic rate |
| title | Phospholipid transfer protein gene knock-out mice have low high density lipoprotein levels, due to hypercatabolism, and accumulate apoA-IV-rich lamellar lipoproteins |
| title_full | Phospholipid transfer protein gene knock-out mice have low high density lipoprotein levels, due to hypercatabolism, and accumulate apoA-IV-rich lamellar lipoproteins |
| title_fullStr | Phospholipid transfer protein gene knock-out mice have low high density lipoprotein levels, due to hypercatabolism, and accumulate apoA-IV-rich lamellar lipoproteins |
| title_full_unstemmed | Phospholipid transfer protein gene knock-out mice have low high density lipoprotein levels, due to hypercatabolism, and accumulate apoA-IV-rich lamellar lipoproteins |
| title_short | Phospholipid transfer protein gene knock-out mice have low high density lipoprotein levels, due to hypercatabolism, and accumulate apoA-IV-rich lamellar lipoproteins |
| title_sort | phospholipid transfer protein gene knock out mice have low high density lipoprotein levels due to hypercatabolism and accumulate apoa iv rich lamellar lipoproteins |
| topic | HDL lipoproteins apolipoproteins phospholipids fractional catabolic rate |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520320617 |
| work_keys_str_mv | AT shucunqin phospholipidtransferproteingeneknockoutmicehavelowhighdensitylipoproteinlevelsduetohypercatabolismandaccumulateapoaivrichlamellarlipoproteins AT koichikawano phospholipidtransferproteingeneknockoutmicehavelowhighdensitylipoproteinlevelsduetohypercatabolismandaccumulateapoaivrichlamellarlipoproteins AT canbruce phospholipidtransferproteingeneknockoutmicehavelowhighdensitylipoproteinlevelsduetohypercatabolismandaccumulateapoaivrichlamellarlipoproteins AT minlin phospholipidtransferproteingeneknockoutmicehavelowhighdensitylipoproteinlevelsduetohypercatabolismandaccumulateapoaivrichlamellarlipoproteins AT charlesbisgaier phospholipidtransferproteingeneknockoutmicehavelowhighdensitylipoproteinlevelsduetohypercatabolismandaccumulateapoaivrichlamellarlipoproteins AT alanrtall phospholipidtransferproteingeneknockoutmicehavelowhighdensitylipoproteinlevelsduetohypercatabolismandaccumulateapoaivrichlamellarlipoproteins AT xianchengjiang phospholipidtransferproteingeneknockoutmicehavelowhighdensitylipoproteinlevelsduetohypercatabolismandaccumulateapoaivrichlamellarlipoproteins |