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  • Title: Age-associated decrease in plasma cholesterol and changes in cholesterol metabolism in homozygous Watanabe heritable hyperlipidemic rabbits.
    Author: Shiomi M, Ito T, Fujioka T, Tsujita Y.
    Journal: Metabolism; 2000 Apr; 49(4):552-6. PubMed ID: 10778885.
    Abstract:
    We examined the cholesterol metabolism of homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model deficient in low-density lipoprotein (LDL) receptors, to clarify the mechanism of the age-associated decrease of plasma total cholesterol, one of the properties of WHHL rabbits. The rabbits were examined at several ages: after weaning at 3 months, at sexual maturation at 6 months, at 12 months, and at 24 months, equivalent to about 35 years of age in humans. Plasma total cholesterol, triglyceride, and phospholipid levels decreased with aging by about 45%. These reductions were mainly dependent on a decrease in the LDL fraction. In the liver microsomal fraction, although there were no age-related changes in the cholesterol concentration and cholesterol 7alpha-hydroxylase (C7H) activity, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity increased and acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity decreased with aging. The lipolytic activity varied with aging. The secretion rate of very-low-density lipoprotein (VLDL) cholesterol as determined by injection of Triton WR-1339 decreased significantly with aging, while the catabolic rate of VLDL cholesterol was about 2-fold higher in the oldest group versus the young groups. From these results, we conclude that the age-associated decrease in plasma cholesterol in WHHL rabbits is related not only to a decrease in the secretion rate of VLDL cholesterol but also to an increase in the catabolic rate.
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