| Apolipoprotein C-III and the metabolic basis for hypertriglyceridemia and the dense low-density lipoprotein phenotype. | |
| | |
MedLine Citation:
|
PMID: 20368524 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Here, we aim to identify defects of apolipoprotein (apo) B lipoprotein metabolism that characterize hypertriglyceridemia, focusing on apoC-III and apoE. METHODS AND RESULTS: We studied the transport of plasma apoB within 21 distinct subfractions as separated by anti-apoC-III and anti-apoE immunoaffinity chromatography and ultracentrifugation in 9 patients with moderate hypertriglyceridemia and 12 normotriglyceridemic control subjects. Hypertriglyceridemia was characterized by a 3-fold higher liver secretion of very low-density lipoprotein (VLDL) that had apoC-III but not apoE and a 50% lower secretion of VLDL with both apoC-III and apoE (both P<0.05). This shift in VLDL secretion pattern from apoE to apoC-III resulted in significantly reduced clearance of light VLDL (-39%; P<0.05), compatible with the antagonizing effects of apoC-III on apoE-induced clearance of triglyceride-rich lipoproteins. In addition, rate constants for clearance were reduced for apoE-containing triglyceride-rich lipoproteins in hypertriglyceridemia, associated with increased apoC-III contents of these particles. LDL distribution shifted from light and medium LDL to dense LDL in hypertriglyceridemia through a quartet of kinetic perturbations: increased flux from apoC-III-containing triglyceride-rich lipoproteins, a shift in liver LDL secretion pattern from light to dense LDL, an increased conversion rate from light and medium LDL to dense LDL, and retarded catabolism of dense LDL. CONCLUSIONS: These results support a central role for apoC-III in metabolic defects leading to hypertriglyceridemia. Triglyceride-rich lipoprotein metabolism shifts from an apoE-dominated system in normotriglyceridemic participants characterized by rapid clearance from circulation of VLDL to an apoC-III-dominated system in hypertriglyceridemic patients characterized by reduced clearance of triglyceride-rich lipoproteins and the formation of the dense LDL phenotype. |
| | |
Authors:
|
Chunyu Zheng; Christina Khoo; Jeremy Furtado; Frank M Sacks |
Related Documents
:
|
15669554 - Randomized trial of effects of estradiol in combination with either norethisterone acet... 3730054 - Quantification and immunolocalization of apolipoprotein e in experimental atherosclerosis. 9260534 - Lipids, apolipoprotein-e genotypes and other risk factors of patients with coronary art... 6501564 - Familial apolipoprotein ai and apolipoprotein ciii deficiency. subclass distribution, c... 11113274 - Antithrombotic potential of olive oil administration in rabbits with elevated cholesterol. 3515374 - Nutritional and social cues influence the onset of puberty in california voles. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-04-05 |
Journal Detail:
|
Title: Circulation Volume: 121 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2010 Apr |
Date Detail:
|
Created Date: 2010-04-20 Completed Date: 2010-05-13 Revised Date: 2011-11-01 |
Medline Journal Info:
|
Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
|
Languages: eng Pagination: 1722-34 Citation Subset: AIM; IM |
Affiliation:
|
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adult Apolipoprotein C-III / metabolism*, secretion Apolipoproteins B / metabolism, secretion Apolipoproteins E / metabolism, secretion Cholesterol, VLDL / metabolism Chromatography, Affinity Dietary Carbohydrates / administration & dosage Dietary Fats / administration & dosage Female Humans Hypertriglyceridemia / metabolism* Leucine / pharmacokinetics Lipoproteins, LDL / biosynthesis, metabolism* Liver / metabolism, secretion Male Middle Aged Phenotype Phenylalanine / pharmacokinetics Triglycerides / metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
P30 DK040561-15/DK/NIDDK NIH HHS; R01 HL056210-03/HL/NHLBI NIH HHS; R01 HL056210-04/HL/NHLBI NIH HHS; R01 HL056210-05/HL/NHLBI NIH HHS; R01 HL070159-01A1/HL/NHLBI NIH HHS; R01 HL070159-02/HL/NHLBI NIH HHS; R01 HL070159-03/HL/NHLBI NIH HHS; R01 HL070159-04/HL/NHLBI NIH HHS; R01-HL-34980/HL/NHLBI NIH HHS; R01-HL-56210/HL/NHLBI NIH HHS; RR02635/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Apolipoprotein C-III; 0/Apolipoproteins B; 0/Apolipoproteins E; 0/Cholesterol, VLDL; 0/Dietary Carbohydrates; 0/Dietary Fats; 0/Lipoproteins, LDL; 0/Triglycerides; 61-90-5/Leucine; 63-91-2/Phenylalanine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Human Adult Vena Saphena Contains Perivascular Progenitor Cells Endowed With Clonogenic and Proangio...
Next Document: Effect of long-term right ventricular pacing in young adults with structurally normal heart.