Effect of Diets on
Lipoprotein Concentrations in Heterozygous Apolipoprotein
E-Deficient Mice
D. BOBKOVÁ, E. HONSOVÁ1, J. KOVÁŘ, R. POLEDNE
Laboratory for Atherosclerosis Research, Institute for Clinical
and Experimental Medicine and Center for Experimental
Cardiovascular Research and 1Department of Pathology
and Anatomy, Institute for Clinical and Experimental Medicine,
Prague, Czech Republic
Received May 12, 2003
Accepted January 8, 2004
Summary
Loss of apolipoprotein E synthesis causes increased serum
cholesterol concentrations and the sensitivity to high-fat diet
in mice. We analyzed the changes in lipoprotein and hepatic
structures in apolipoprotein E-deficient mice kept on control
diet and cholesterol diets. Basal cholesterolemia of
heterozygous (+/-) mice (2.2±0.28 mmol/l) was the same compared
to wild-type (+/+) mice (2.3±0.15 mmol/l), but was lower
compared to homozygous (-/-) mice (10.3±1.40 mmol/l). In +/-
mice, cholesterolemia rose to 3.2 mmol/l on cholesterol diet and
to 9 mmol/l on cholate diet, to 3 mmol/l and 3.6 mmol/l in +/+
mice, and to 23.4 mmol/l and 70.5 mmol/l in -/- mice,
respectively. While the ratio of cholesterol/triglyceride
concentrations in VLDL, IDL and LDL fractions was not increased
in +/- mice and +/+ mice, it was increased in -/- mice on
control diet. On the cholesterol diet, this ratio rose and was
dramatically increased by cholate diet in all groups of mice.
Even though cholate supplementation increased cholesterol
concentration, it led to substantial toxic changes in hepatic
morphology of all animals. In conclusion, one functional apo E
allele in +/- mice is effective in keeping serum cholesterol
concentrations in normal range on a control diet, but not on the
cholesterol and cholate diets.
Key words
Apolipoprotein E • Heterozygous mice • Hyperlipoproteinemia •
Hepatotoxicity
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