Increased response to cholesterol feeding in apolipoprotein C1-deficient mice

J. H. Van Ree, M. H. Hofker, J. A A Van den Broek, Jan Van Deursen, H. Van der Boom, R. R. Frants, B. Wieringa, L. M. Havekes

Research output: Contribution to journalArticle

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Abstract

The function of apolipoprotein (apo) C1 in vivo is not well understood. From in vitro studies it has been reported that an excess of apoC1 relative to apoE inhibits receptor-mediated uptake of remnant lipoproteins. In order to gain a better understanding of the role of apoC1 in lipoprotein metabolism in vivo, we have generated apoC1-deficient mice by gene targeting in embryonic stem cells. Homozygous mutant mice are viable and do not show overt abnormalities. Serum triacylglycerol levels are increased by 60% on both a standard mouse diet and a mild hypercholesterolaemic diet compared with controls. Total serum cholesterol levels are similar to controls on the two diets. However, the level of high-density lipoprotein cholesterol in the apoC1-deficient mice fed on the mild hypercholesterolaemic diet is slightly decreased, which is accompanied by a 3-fold increase in very-low-density plus low-density lipoprotein (VLDL + LDL) cholesterol. On a severe atherogenic diet, the homozygous apoC1-deficient mice become hypercholesterolaemic, with a serum cholesterol level of 10.7 ± 3.3 mM compared with 6.7 ± 1.8 mM and 5.1 ± 1.6 mM in heterozygous and control mice respectively. The increase in cholesterol is mainly confined to the VLDL + LDL-sized fractions. Binding experiments revealed that lipoproteins lacking apoC1 with d < 1.006 g/ml are poor competitors for 125I-labelled LDL binding to the LDL receptor on HepG2 cells. This suggests that total apoC1 deficiency leads to impaired receptor-mediated clearance of remnant lipoproteins rather than enhanced uptake, as was expected from data reported in the literature.

Original languageEnglish (US)
Pages (from-to)905-911
Number of pages7
JournalBiochemical Journal
Volume305
Issue number3
StatePublished - 1995
Externally publishedYes

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Apolipoprotein C-I
Nutrition
Cholesterol
Lipoproteins
Diet
Serum
Low Density Lipoprotein Receptor-Related Protein-1
Atherogenic Diet
LDL Receptors
Apolipoproteins E
VLDL Cholesterol
Stem cells
LDL Lipoproteins
Gene Targeting
Metabolism
LDL Cholesterol
HDL Cholesterol
Hep G2 Cells
Embryonic Stem Cells
Triglycerides

ASJC Scopus subject areas

  • Biochemistry

Cite this

Van Ree, J. H., Hofker, M. H., Van den Broek, J. A. A., Van Deursen, J., Van der Boom, H., Frants, R. R., ... Havekes, L. M. (1995). Increased response to cholesterol feeding in apolipoprotein C1-deficient mice. Biochemical Journal, 305(3), 905-911.

Increased response to cholesterol feeding in apolipoprotein C1-deficient mice. / Van Ree, J. H.; Hofker, M. H.; Van den Broek, J. A A; Van Deursen, Jan; Van der Boom, H.; Frants, R. R.; Wieringa, B.; Havekes, L. M.

In: Biochemical Journal, Vol. 305, No. 3, 1995, p. 905-911.

Research output: Contribution to journalArticle

Van Ree, JH, Hofker, MH, Van den Broek, JAA, Van Deursen, J, Van der Boom, H, Frants, RR, Wieringa, B & Havekes, LM 1995, 'Increased response to cholesterol feeding in apolipoprotein C1-deficient mice', Biochemical Journal, vol. 305, no. 3, pp. 905-911.
Van Ree JH, Hofker MH, Van den Broek JAA, Van Deursen J, Van der Boom H, Frants RR et al. Increased response to cholesterol feeding in apolipoprotein C1-deficient mice. Biochemical Journal. 1995;305(3):905-911.
Van Ree, J. H. ; Hofker, M. H. ; Van den Broek, J. A A ; Van Deursen, Jan ; Van der Boom, H. ; Frants, R. R. ; Wieringa, B. ; Havekes, L. M. / Increased response to cholesterol feeding in apolipoprotein C1-deficient mice. In: Biochemical Journal. 1995 ; Vol. 305, No. 3. pp. 905-911.
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