Regulation Of Plasma Cholesterol Levels Research Articles

Low density lipoprotein metabolism in the normal to moderately elevated range of plasma cholesterol: comparisons with familial hypercholesterolemia

Low density lipoprotein (LDL) metabolism was investigated using a pulse injection of 125I-labeled LDL in 20 subjects who did not have familial hypercholesterolemia (FH) (plasma cholesterol 160-297 mg/dl) and in 9 subjects who did have heterozygous FH (plasma cholesterol 273-501 mg/dl). Subjects were also injected with 131I-labeled LDL chemically modified with cyclohexanedione. This technique permitted a calculation of the amount of apoLDL removed via receptor-mediated and receptor-independent pathways. In subjects without FH, 40% (range 25-49%) of LDL was cleared via receptor-mediated pathways and in subjects with FH this figure was 22% (range 3-33%). In nonfamilial hypercholesterolemia there was clear evidence of defective removal of LDL via receptor-independent pathways in association with some overproduction of apoLDL. In heterozygous FH there was evidence of defective removal of LDL via receptor-mediated pathways, while some subjects also showed evidence of overproduction of apoLDL. It is suggested that LDL catabolism via receptor-independent pathways plays a major role in regulating plasma cholesterol levels in the normal to moderately elevated range.

Studies on the regulation of plasma cholesterol levels in squirrel monkeys of two genotypes

Certain individual squirrel monkeys ("hypo-responders") are able to remain normocholesterolemic when fed diets containing cholesterol (0.5 mg/kcal). Other squirrel monkeys ("hyperresponders") when fed the same diet become hypercholesterolemic. The purpose of these studies was to identify the mechanisms which allow hyporesponders to compensate for dietary cholesterol. Using formula diets and sterol balance techniques, we have compared cholesterol absorption, synthesis, excretion, and turnover in hypo- and hyperresponding monkeys. Cholesterol absorption was essentially identical in the two groups (about 55 mg/day). Cholesterol synthesis was likewise similar in the two groups (about 35 mg/day) and there was no evidence of feedback inhibition at the level of cholesterol fed. Hyporesponders had faster turnover rates and smaller body cholesterol pools than did hyperresponders. Excretion of neutral steroids was similar for hypo- and hyperresponders and did not change with cholesterol feeding. In contrast, hyporesponders increased bile acid excretion shortly after cholesterol feeding was begun. Hyperresponders responded more slowly and to a lesser degree. It is concluded that, in this species, the mechanism of control of plasma cholesterol levels is related to the rate of conversion of cholesterol to bile acids.