Overexpression ofapoC-III produces lesser hypertriglyceridemia in apoB-48-only gene-targeted micethan in apoB-100-only mice

The adaptive value of apolipoprotein B-48 (apoB-48), thetruncated form of apoB produced by the intestine, in lipid metabolism remainsunclear. We crossed human apoC-III transgenic mice with mice expressing eitherapoB-48 only (apoB48/48) or apoB-100 only(apoB100/100). Cholesterol levels were higher in...

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Main Authors: Karin Conde-Knape, Kenta Okada, Rajasekhar Ramakrishnan, NeilS. Shachter
Format: Article
Language:English
Published: Elsevier 2004-12-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520341031
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author Karin Conde-Knape
Kenta Okada
Rajasekhar Ramakrishnan
NeilS. Shachter
author_facet Karin Conde-Knape
Kenta Okada
Rajasekhar Ramakrishnan
NeilS. Shachter
author_sort Karin Conde-Knape
collection DOAJ
description The adaptive value of apolipoprotein B-48 (apoB-48), thetruncated form of apoB produced by the intestine, in lipid metabolism remainsunclear. We crossed human apoC-III transgenic mice with mice expressing eitherapoB-48 only (apoB48/48) or apoB-100 only(apoB100/100). Cholesterol levels were higher inapoB48/48 mice than in apoB100/100 micebut triglyceride levels were similar. Lipid levels were increased by the apoC-IIItransgene. However, triglyceride levels were significantly higher inapoB100/100C-III than in apoB48/48C-IIImice (895 ± 395 mg/dl vs. 690 ± 252 mg/dl; P <0.01), whereas cholesterol levels were higher in theapoB48/48C-III mice than inapoB100/100C-III (144 ± 35 mg/dl vs. 94 ± 30mg/dl; P < 0.00001). Triglyceride clearance from VLDL wasimpaired to a greater extent in apoB100/100C-III vs.apoB100/100 mice than in apoB48/48C-IIIvs. apoB48/48 mice. Triglyceride secretion rates were nodifferent in apoC-III transgenic mice than in their nontransgenic littermates.ApoB-48 triglyceride-rich lipoproteins were more resistant to thetriglyceride-increasing effects of apoC-III but appeared more sensitive to theremnant clearance inhibition.Our findings support a coordinated role forapoB-48 in facilitating the delivery of dietary triglycerides to the periphery.Consistent with such a mechanism, glucose levels were significantly higher inapoB48/48 mice vs. apoB100/100 mice,perhaps on the basis of metabolic competition.
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spelling doaj.art-18e969c5ab2045febd5d3490248f486d2022-12-21T18:55:37ZengElsevierJournal of Lipid Research0022-22752004-12-01451222352244Overexpression ofapoC-III produces lesser hypertriglyceridemia in apoB-48-only gene-targeted micethan in apoB-100-only miceKarin Conde-Knape0Kenta Okada1Rajasekhar Ramakrishnan2NeilS. Shachter3Department of Medicine, Columbia University, New York, NY10032; Department of Pediatrics, Columbia University, NewYork, NY 10032Department of Medicine, Columbia University, New York, NY10032; Department of Pediatrics, Columbia University, NewYork, NY 10032Department of Medicine, Columbia University, New York, NY10032; Department of Pediatrics, Columbia University, NewYork, NY 10032Department of Medicine, Columbia University, New York, NY10032; Department of Pediatrics, Columbia University, NewYork, NY 10032The adaptive value of apolipoprotein B-48 (apoB-48), thetruncated form of apoB produced by the intestine, in lipid metabolism remainsunclear. We crossed human apoC-III transgenic mice with mice expressing eitherapoB-48 only (apoB48/48) or apoB-100 only(apoB100/100). Cholesterol levels were higher inapoB48/48 mice than in apoB100/100 micebut triglyceride levels were similar. Lipid levels were increased by the apoC-IIItransgene. However, triglyceride levels were significantly higher inapoB100/100C-III than in apoB48/48C-IIImice (895 ± 395 mg/dl vs. 690 ± 252 mg/dl; P <0.01), whereas cholesterol levels were higher in theapoB48/48C-III mice than inapoB100/100C-III (144 ± 35 mg/dl vs. 94 ± 30mg/dl; P < 0.00001). Triglyceride clearance from VLDL wasimpaired to a greater extent in apoB100/100C-III vs.apoB100/100 mice than in apoB48/48C-IIIvs. apoB48/48 mice. Triglyceride secretion rates were nodifferent in apoC-III transgenic mice than in their nontransgenic littermates.ApoB-48 triglyceride-rich lipoproteins were more resistant to thetriglyceride-increasing effects of apoC-III but appeared more sensitive to theremnant clearance inhibition.Our findings support a coordinated role forapoB-48 in facilitating the delivery of dietary triglycerides to the periphery.Consistent with such a mechanism, glucose levels were significantly higher inapoB48/48 mice vs. apoB100/100 mice,perhaps on the basis of metabolic competition.http://www.sciencedirect.com/science/article/pii/S0022227520341031apolipoproteins CapolipoproteinsBhyperglycemiatransgenicpostprandialperiod
spellingShingle Karin Conde-Knape
Kenta Okada
Rajasekhar Ramakrishnan
NeilS. Shachter
Overexpression ofapoC-III produces lesser hypertriglyceridemia in apoB-48-only gene-targeted micethan in apoB-100-only mice
Journal of Lipid Research
apolipoproteins C
apolipoproteinsB
hyperglycemia
transgenic
postprandialperiod
title Overexpression ofapoC-III produces lesser hypertriglyceridemia in apoB-48-only gene-targeted micethan in apoB-100-only mice
title_full Overexpression ofapoC-III produces lesser hypertriglyceridemia in apoB-48-only gene-targeted micethan in apoB-100-only mice
title_fullStr Overexpression ofapoC-III produces lesser hypertriglyceridemia in apoB-48-only gene-targeted micethan in apoB-100-only mice
title_full_unstemmed Overexpression ofapoC-III produces lesser hypertriglyceridemia in apoB-48-only gene-targeted micethan in apoB-100-only mice
title_short Overexpression ofapoC-III produces lesser hypertriglyceridemia in apoB-48-only gene-targeted micethan in apoB-100-only mice
title_sort overexpression ofapoc iii produces lesser hypertriglyceridemia in apob 48 only gene targeted micethan in apob 100 only mice
topic apolipoproteins C
apolipoproteinsB
hyperglycemia
transgenic
postprandialperiod
url http://www.sciencedirect.com/science/article/pii/S0022227520341031
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