VLDL and IDL apolipoprotein B-100 kinetics in familial hypercholesterolemia due to impaired LDL receptor function or to defective apolipoprotein B-100
Mutations in the apolipoprotein (apo) B, E (LDL) receptor gene and in the apolipoprotein B-100 gene are the cause of familial hypercholesterolemia (FH) and of familial defective apo B-100 (FDB), respectively. Whether these abnormalities lead to altered production or uptake of very low density lipopr...
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| Format: | Article |
| Language: | English |
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Elsevier
1998-02-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520338992 |
| _version_ | 1818384893158096896 |
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| author | Henryk Zulewski Ron Ninnis André R. Miserez Manfred W. Baumstark Ulrich Keller |
| author_facet | Henryk Zulewski Ron Ninnis André R. Miserez Manfred W. Baumstark Ulrich Keller |
| author_sort | Henryk Zulewski |
| collection | DOAJ |
| description | Mutations in the apolipoprotein (apo) B, E (LDL) receptor gene and in the apolipoprotein B-100 gene are the cause of familial hypercholesterolemia (FH) and of familial defective apo B-100 (FDB), respectively. Whether these abnormalities lead to altered production or uptake of very low density lipoprotein (VLDL) or intermediate density lipoprotein (IDL) has not been established previously. Therefore VLDL and IDL apo B-100 kinetics were measured in seven subjects with FH, in six subjects with FDB, and in five normocholesterolemic controls using primed-constant infusions of [1-13C]leucine. Absolute production rates (APR) of VLDL apoB were higher in FH than in controls (27.1 ± 1.9 vs. 17.9 ± 2.1 mg/kg/day P < 0.03). VLDL APR in FDB were between those of FH and controls (24.3 ± 4.8 mg/kg/day), and demonstrated a relatively large inter-individual variability. The increase in VLDL APR in FH resulted in higher fasting serum triglyceride concentrations than in controls (P < 0.05), whereas in FDB triglycerides were between those observed in FH and in controls. A significant correlation was observed between VLDL apoB APR and serum triglycerides in FH and in FDB; the correlation coefficient for all subjects was r = 0.84 (P < 0.0001), indicating that the major determinant of serum triglyceride concentrations was VLDL apoB APR. IDL apoB APR was lower in FH and in FDB compared to controls (P < 0.03 P < 0.02, respectively): and its fractional catabolic rate (FCR) was slightly lower in FH and in FDB, resulting in similar plasma IDL apoB concentrations in all three groups of subjects. IDL apoB APR in FH were negatively correlated with LDL cholesterol concentrations (r = –0.89; P < 0.001); LDL cholesterol concentrations correlated positively with the part of VLDL that did not appear in IDL (r = 0.82 P < 0.02), bypassing therefore the delipidation cascade. In conclusion the data demonstrate increased VLDL apoB production rates in FH. VLDL and IDL kinetics differ when LDL concentrations are elevated either due to a LDL receptor defect or due to defective apolipoprotein B-100.—Zulewski H., R. Ninnis, A. R. Miserez, M. W. Baumstark, and U. Keller. VLDL and IDL apolipoprotein B-100 kinetics in familial hypercholesterolemia due to impaired LDL receptor function or to defective apolipoprotein B-100. |
| first_indexed | 2024-12-14T03:29:29Z |
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| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T03:29:29Z |
| publishDate | 1998-02-01 |
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| spelling | doaj.art-baad0b55088e4ef4ad7d47cb952caffb2022-12-21T23:18:47ZengElsevierJournal of Lipid Research0022-22751998-02-01392380387VLDL and IDL apolipoprotein B-100 kinetics in familial hypercholesterolemia due to impaired LDL receptor function or to defective apolipoprotein B-100Henryk Zulewski0Ron Ninnis1André R. Miserez2Manfred W. Baumstark3Ulrich Keller4Division of Endocrinology, Diabetes, and Clinical Nutrition, and Department of Research, University Hospital of Basel, Petersgraben 4, CH-4031 Basel, SwitzerlandDivision of Endocrinology, Diabetes, and Clinical Nutrition, and Department of Research, University Hospital of Basel, Petersgraben 4, CH-4031 Basel, SwitzerlandDivision of Endocrinology, Diabetes, and Clinical Nutrition, and Department of Research, University Hospital of Basel, Petersgraben 4, CH-4031 Basel, SwitzerlandDepartment of Sports Medicine, Albert Ludwigs-University, D-79106 Freiburg, GermanyDivision of Endocrinology, Diabetes, and Clinical Nutrition, and Department of Research, University Hospital of Basel, Petersgraben 4, CH-4031 Basel, Switzerland; To whom correspondence should be addressed.Mutations in the apolipoprotein (apo) B, E (LDL) receptor gene and in the apolipoprotein B-100 gene are the cause of familial hypercholesterolemia (FH) and of familial defective apo B-100 (FDB), respectively. Whether these abnormalities lead to altered production or uptake of very low density lipoprotein (VLDL) or intermediate density lipoprotein (IDL) has not been established previously. Therefore VLDL and IDL apo B-100 kinetics were measured in seven subjects with FH, in six subjects with FDB, and in five normocholesterolemic controls using primed-constant infusions of [1-13C]leucine. Absolute production rates (APR) of VLDL apoB were higher in FH than in controls (27.1 ± 1.9 vs. 17.9 ± 2.1 mg/kg/day P < 0.03). VLDL APR in FDB were between those of FH and controls (24.3 ± 4.8 mg/kg/day), and demonstrated a relatively large inter-individual variability. The increase in VLDL APR in FH resulted in higher fasting serum triglyceride concentrations than in controls (P < 0.05), whereas in FDB triglycerides were between those observed in FH and in controls. A significant correlation was observed between VLDL apoB APR and serum triglycerides in FH and in FDB; the correlation coefficient for all subjects was r = 0.84 (P < 0.0001), indicating that the major determinant of serum triglyceride concentrations was VLDL apoB APR. IDL apoB APR was lower in FH and in FDB compared to controls (P < 0.03 P < 0.02, respectively): and its fractional catabolic rate (FCR) was slightly lower in FH and in FDB, resulting in similar plasma IDL apoB concentrations in all three groups of subjects. IDL apoB APR in FH were negatively correlated with LDL cholesterol concentrations (r = –0.89; P < 0.001); LDL cholesterol concentrations correlated positively with the part of VLDL that did not appear in IDL (r = 0.82 P < 0.02), bypassing therefore the delipidation cascade. In conclusion the data demonstrate increased VLDL apoB production rates in FH. VLDL and IDL kinetics differ when LDL concentrations are elevated either due to a LDL receptor defect or due to defective apolipoprotein B-100.—Zulewski H., R. Ninnis, A. R. Miserez, M. W. Baumstark, and U. Keller. VLDL and IDL apolipoprotein B-100 kinetics in familial hypercholesterolemia due to impaired LDL receptor function or to defective apolipoprotein B-100.http://www.sciencedirect.com/science/article/pii/S0022227520338992apolipoprotein B-100VLDLIDLLDLFHFDB |
| spellingShingle | Henryk Zulewski Ron Ninnis André R. Miserez Manfred W. Baumstark Ulrich Keller VLDL and IDL apolipoprotein B-100 kinetics in familial hypercholesterolemia due to impaired LDL receptor function or to defective apolipoprotein B-100 Journal of Lipid Research apolipoprotein B-100 VLDL IDL LDL FH FDB |
| title | VLDL and IDL apolipoprotein B-100 kinetics in familial hypercholesterolemia due to impaired LDL receptor function or to defective apolipoprotein B-100 |
| title_full | VLDL and IDL apolipoprotein B-100 kinetics in familial hypercholesterolemia due to impaired LDL receptor function or to defective apolipoprotein B-100 |
| title_fullStr | VLDL and IDL apolipoprotein B-100 kinetics in familial hypercholesterolemia due to impaired LDL receptor function or to defective apolipoprotein B-100 |
| title_full_unstemmed | VLDL and IDL apolipoprotein B-100 kinetics in familial hypercholesterolemia due to impaired LDL receptor function or to defective apolipoprotein B-100 |
| title_short | VLDL and IDL apolipoprotein B-100 kinetics in familial hypercholesterolemia due to impaired LDL receptor function or to defective apolipoprotein B-100 |
| title_sort | vldl and idl apolipoprotein b 100 kinetics in familial hypercholesterolemia due to impaired ldl receptor function or to defective apolipoprotein b 100 |
| topic | apolipoprotein B-100 VLDL IDL LDL FH FDB |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520338992 |
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