Effects of dietary hypercholesterolemia on plasma lipids levels male and female Japanese white and heterozygous Kurosawa-Kusanagi hypercholesterolemic rabbits

Abstract

High plasma cholesterol levels constitute a major risk factor for coronary heart diseases. In this study, we compared the response to dietary hypercholesterolemia with respect to plasma lipids levels in male and female Kurosawa-Kusanagi hypercholesterolemic (KHC) rabbits, which have Low density lipoprotein (LDL) receptor deficiency. Male and female Japanese white (JW) and heterozygous KHC rabbits were given a standard milled rabbit diet or diets with different concentrations of cholesterol. All the male and female JW and KHC rabbits given a standard milled rabbit diet did not show increased plasma cholesterol levels over the 24-week experiments. The plasma cholesterol levels in male JW rabbits fed a 0.1 % cholesterol-containing diet did not increase, but the levels in male heterozygous KHC rabbits fed the same diet transiently increased for 4-8 weeks (to 300 mg/dL) and then gradually decreased till the initial level. In contrast, in female JW rabbits fed the same diet, the plasma cholesterol  levels increased for 4-24 weeks (to 300 mg/dL), and in heterozygous KHC rabbits, the levels gradually increased (to 675 mg/dL after 24 weeks) after consumption of the 0.1 % cholesterol-containing diet. In ovariectomized JW and KHC rabbits fed the 0.1 % cholesterol-containing diet, the plasma cholesterol levels were half value the levels in non-ovariectomized rabbits  after 24 weeks. Gene expression of the LDL receptor in the liver significantly increased in male JW and KHC rabbits, but significantly decreased in female KHC rabbits. These results indicate that female rabbits had a greater response to the cholesterol diet than male rabbits and that the responsiveness to dietary hypercholesterolemia was predominantly genetic.