Physiol. Res. 53: 635-643, 2004

Effect of Diets on Lipoprotein Concentrations in Heterozygous Apolipoprotein E-Deficient Mice


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

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

© 2004 by the Institute of Physiology, Czech Academy of Sciences