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ApoB-48 and apoB-100 differentially influence the expression of type-III hyperlipoproteinemia in APOE*2 mice.

Publication ,  Journal Article
Hinsdale, ME; Sullivan, PM; Mezdour, H; Maeda, N
Published in: J Lipid Res
September 2002

Apolipoprotein E (apoE) is essential for the clearance of plasma chylomicron and VLDL remnants. The human APOE locus is polymorphic and 5-10% of APOE*2 homozygotes exhibit type-III hyperlipoproteinemia (THL), while the remaining homozygotes have less than normal plasma cholesterol. In contrast, mice expressing APOE*2 in place of the mouse Apoe (Apoe(2/2) mice) are markedly hyperlipoproteinemic, suggesting a species difference in lipid metabolism (e.g., editing of apolipoprotein B) enhances THL development. Since apoB-100 has an LDLR binding site absent in apoB-48, we hypothesized that the Apoe(2/2) THL phenotype would improve if all Apoe(2/2) VLDL contained apoB-100. To test this, we crossed Apoe(2/2) mice with mice lacking the editing enzyme for apoB (Apobec(-/-)). Consistent with an increase in remnant clearance, Apoe(2/2). Apobec(-/-) mice have a significant reduction in IDL/LDL cholesterol (IDL/LDL-C) compared with Apoe(2/2) mice. However, Apoe(2/2).Apobec(-/-) mice have twice as much VLDL triglyceride as Apoe(2/2) mice. In vitro tests show the apoB-100-containing VLDL are poorer substrates for lipoprotein lipase than apoB-48-containing VLDL. Thus, despite a lowering in IDL/LDL-C, substituting apoB-48 lipoproteins with apoB-100 lipoproteins did not improve the THL phenotype in the Apoe(2/2).Apobec(-/-) mice, because apoB-48 and apoB-100 differentially influence the catabolism of lipoproteins.

Duke Scholars

Published In

J Lipid Res

DOI

ISSN

0022-2275

Publication Date

September 2002

Volume

43

Issue

9

Start / End Page

1520 / 1528

Location

United States

Related Subject Headings

  • Triglycerides
  • Phenotype
  • Mice, Knockout
  • Mice
  • Male
  • Lipoproteins, VLDL
  • Hyperlipoproteinemia Type III
  • Female
  • Electrophoresis, Polyacrylamide Gel
  • Blotting, Western
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Hinsdale, M. E., Sullivan, P. M., Mezdour, H., & Maeda, N. (2002). ApoB-48 and apoB-100 differentially influence the expression of type-III hyperlipoproteinemia in APOE*2 mice. J Lipid Res, 43(9), 1520–1528. https://doi.org/10.1194/jlr.m200103-jlr200
Hinsdale, Myron E., Patrick M. Sullivan, Hafid Mezdour, and Nobuyo Maeda. “ApoB-48 and apoB-100 differentially influence the expression of type-III hyperlipoproteinemia in APOE*2 mice.J Lipid Res 43, no. 9 (September 2002): 1520–28. https://doi.org/10.1194/jlr.m200103-jlr200.
Hinsdale ME, Sullivan PM, Mezdour H, Maeda N. ApoB-48 and apoB-100 differentially influence the expression of type-III hyperlipoproteinemia in APOE*2 mice. J Lipid Res. 2002 Sep;43(9):1520–8.
Hinsdale, Myron E., et al. “ApoB-48 and apoB-100 differentially influence the expression of type-III hyperlipoproteinemia in APOE*2 mice.J Lipid Res, vol. 43, no. 9, Sept. 2002, pp. 1520–28. Pubmed, doi:10.1194/jlr.m200103-jlr200.
Hinsdale ME, Sullivan PM, Mezdour H, Maeda N. ApoB-48 and apoB-100 differentially influence the expression of type-III hyperlipoproteinemia in APOE*2 mice. J Lipid Res. 2002 Sep;43(9):1520–1528.

Published In

J Lipid Res

DOI

ISSN

0022-2275

Publication Date

September 2002

Volume

43

Issue

9

Start / End Page

1520 / 1528

Location

United States

Related Subject Headings

  • Triglycerides
  • Phenotype
  • Mice, Knockout
  • Mice
  • Male
  • Lipoproteins, VLDL
  • Hyperlipoproteinemia Type III
  • Female
  • Electrophoresis, Polyacrylamide Gel
  • Blotting, Western