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Extensive data obtained in both experimental animals and humans demonstrate that steady-state plasma LDL-C concentrations are determined largely by the rate of LDL-C formation, Jt, and the level of LDL-R activity, Jm, located primarily in the liver. An increase in net cholesterol delivery to the liver suppresses Jm, slightly elevates Jt, and modestly raises(More)
This study was undertaken to measure and compare the rates at which digitonin-precipitable sterols (DPS) were synthesized in vivo in the major organs of five different animal species. These rates were assessed by measuring the velocity at which [3H]water was incorporated into DPS in the intact animal. The animals used were chosen to include species that(More)
In vivo regulation of hepatic sterol metabolism was examined in the rat. Sodium cholate markedly suppressed hepatic 7 alpha-hydroxylase mRNA levels and activity when fed to rats on a low cholesterol diet. Sterol balance was maintained solely by decreasing hepatic cholesterol synthesis. Compensatory mechanisms were inadequate when cholate was fed to rats on(More)
This study was undertaken to determine the effect of transient overexpression of hepatic cholesterol 7alpha-hydroxylase on low density lipoprotein (LDL) cholesterol transport in mice lacking LDL receptors (LDL receptor-/-). Primary overexpression of hepatic 7alpha-hydroxylase in LDL receptor-/- mice was accompanied by a dose-dependent decrease in the rate(More)
These studies were carried out in order to examine the relationship between the rate of uptake of low-density lipoproteins (LDL) by the liver and the rates of hepatic and extrahepatic cholesterol synthesis and biliary cholesterol content. Female hamsters fed a regular chow diet manifested a rate of hepatic sterol synthesis that was several-fold higher than(More)
These studies were done to determine whether an underlying metabolic difference could account for the higher concentration of cholesterol carried in low density lipoproteins (LDL-C) in male hyperresponder (HR) cynomolgus monkeys than in their hyporesponder (HO) counterparts during dietary cholesterol challenge. All animals were fed to steady state at 5(More)
The suitability of the adult male cynomolgus monkey as a model for investigating genetic mechanisms that regulate dietary cholesterolemic response was evaluated by carrying out a systematic characterization of the major aspects of cholesterol metabolism in this species. In monkeys maintained on a diet enriched with saturated fat but low in cholesterol(More)
These studies examine the regulation of plasma low density lipoprotein (LDL)-cholesterol levels by varying quantities of dietary saturated and polyunsaturated triacylglycerols. At a constant load of 0.12% cholesterol and 20% triacylglycerol, substitution of polyunsaturated for saturated triacylglycerols caused LDL receptor activity to increase from 25% to(More)