Cholesterol feeding increases low density lipoprotein synthesis.

Abstract

A B S T R A C T This study examines the effects of increased dietary cholesterol (6 eggs/d) on the metabolism of low density lipoproteins in a group of seven healthy volunteers. Egg supplementation raised high density and low density lipoprotein cholesterol levels by 18 and 40%, respectively. The composition of the low density lipoprotein was unaltered and therefore the number of circulating particles must have increased. Kinetic studies indicated that this was due primarily to a 23% rise in the rate of synthesis of the lipoprotein. Catabolism was also affected. The fractional removal rate of native low density lipoprotein fell by 10% (P < 0.05). However, the clearance of the 1,2 cyclohexanedione-treated lipoprotein remained unchanged (control fractional clearance rate [FCR] = 0.188 pools/d; cholesterol feeding FCR = 0.183 pools/d). Therefore, the reduction in low density lipoprotein catabolism appeared to be due to a fall in receptor activity. Consequently, an increased sterol load (34.2 gmol/kg per d vs. 27.7 umol/kg per d in the control phase, P < 0.02) was channelled into the receptor-independent route during egg feeding.

Relationship between sensitivity to dietary fat and dietary cholesterol.

“…3334 Factors associated with both the production and the removal of lipoproteins are likely to be involved. Down-regulation of LDL receptors occurs with high cholesterol intakes 35 ; a similar response has been noted for saturated fat only in hamsters, 38 and not in humans. Since excess dietary cholesterol induces increased hepatic secretion of IDL 37 and of LDL, 38 responsiveness may reflect the capacity of removal mechanisms to clear the influx of lipoprotein.…”

“…Down-regulation of LDL receptors occurs with high cholesterol intakes 35 ; a similar response has been noted for saturated fat only in hamsters, 38 and not in humans. Since excess dietary cholesterol induces increased hepatic secretion of IDL 37 and of LDL, 38 responsiveness may reflect the capacity of removal mechanisms to clear the influx of lipoprotein. Similarly, saturated fatty acids induce higher LDL secretion rates in humans 39 and greater triglyceride synthesis in rat liver 40 than do more unsaturated fatty acids.…”

Low-density lipoprotein receptor-mediated delivery of a lipophilic daunorubicin derivative to B16 tumours in mice using apolipoprotein E-enriched liposomes

“…precautions are necessary to protect these organs from irreversible tissue damage. Expression of LDL receptors in the liver can be decreased by a diet enriched in cholesterol and triglycerides rich in saturated fatty acids (Angelin et al 1983: Dietschy et al 1993: Packard et al 1983). The expression of LDL receptors in the spleen and adrenals can be significantly reduced by the administration of bile salts and corticosteroids respectively (Hynds et al, 1984: Isaacsohn et al 1986).…”

Contribution of the receptor pathway to low density lipoprotein catabolism in humans. New methods for quantitation.

“…7 In fact, direct comparison of the clearances of HOET-LDL and CHD-LDL showed that their metabolic properties were indistinguishable ( Figure 6, Table 5). So in this regard, CHD-LDL metabolism seems to differ in humans and in rabbits.…”

“…We used 1,2 cyclohexanedione (CHD) to block the guanido group of arginyl residues on LDL apoprotein (apo LDL), and found that the receptor pathway accounted for between 35% and 50% of LDL catabolism in normal subjects. 6 ' 7 This value was reduced in familial hypercholesterolemic patients 68 whose cell membrane receptors for LDL are defective or absent. The use of the CHD-LDL probe, however, was open to the criticism that the modification is unstable.…”