title: Age-associated decrease in plasma cholesterol and changes in cholesterol metabolism in homozygous Watanabe heritable hyperlipidemic rabbits.
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.
authors.affiliation: Institute for Experimental Animals, Kobe University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shiomi
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Fujioka
authors.forename: Y
authors.initials: Y
authors.lastname: Tsujita
mesh_terms: D000375:Aging / Q000097:blood*; D000818:Animals; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D006720:Homozygote; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000097:blood; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008861:Microsomes / Q000201:enzymology; D009994:Osmolar Concentration; D011817:Rabbits
chemical_list: D008055:Lipids; D008079:Lipoproteins, VLDL; D002784:Cholesterol; D008049:Lipase; D008071:Lipoprotein Lipase