Long-term decay of serum cholesterol radioactivity: body cholesterol metabolism in normals and in patients with hyperlipoproteinemia and atherosclerosis

A B S T R A C T Long-term studies (32-49 wk) of the turnover of plasma cholesterol were conducted in 24 subjects. Eight subjects were normolipidemic, six had hypercholesterolemia, eight had hypercholesterolemia and hypertriglyceridemia, and two had hypertriglyceridemia alone. 10 of the hyperlipidemic patients had a definite familial disorder. In all subjects (except one for whom complete data were not available), the same three-pool model previously described gave the best fit for the data. Ml was correlated with all body size variables, but most strongly with excess weight. After adjusting for the effects of body size, M1 was also correlated with the serum concentrations of both cholesterol and triglyceride. Major differences were found in the relationships between the physiological variables and the sizes of pools 2 and 3. M2 was correlated neither with any of the indices of body size or adiposity, nor with the serum levels of either cholesterol or triglyceride. In contrast, all estimates of M3 were correlated with indices of adiposity (but not of overall body size) and with the serum cholesterol concentration.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Parameters of the three-pool model of the turnover of plasma cholesterol in normal and hyperlipidemic humans.

Smith¹,

Dell²,

Noble³

et al. 1976

“…Despite this, the cholesterol content of extrahepatic tissues, measured directly in biopsies (13,14) or indirectly by isotope dilution analysis (15)(16)(17), has been only weakly correlated with the plasma total and LDL cholesterol concentrations. On the other hand, a recent study of hyperlipidemic subjects established that body cholesterol pool size shows a strong negative correlation with the plasma high density lipoprotein (HDL) concentration (17).…”

Section: Introductionmentioning

confidence: 99%

Interaction between High Density and Low Density Lipoproteins during Uptake and Degradation by Cultured Human Fibroblasts

Miller¹,

Weinstein²,

Carew³

et al. 1977

107

A B S T RA CT High density lipoprotein (HDL) inhibited the binding (trypsin-releasable radioactivity), internalization (cell-associated radioactivity after trypsinization), and degradation (TCA-soluble noniodide radioactivity) of 1251-low density lipoprotein (1251-LDL) by cultured normal human fibroblasts. At HDL:LDL molar ratios of 25:1 (protein ratios about 5:1), these parameters were reduced by about 25%. Unlabeled LDL was about 25 times more effective in reducing 125I-LDL binding, implying that if HDL and LDL bind at common sites the affinity of HDL for these sites is very low or that the interaction is on some other basis. The fractional reduction in 125I_ LDL binding at a given HDL: 1251-LDL ratio was independent of '25I-LDL concentration and occurred equally with fibroblasts from a subject with homozygous familial hypercholesterolemia. Reciprocally, the binding, internalization, and degradation of 125I_ HDL were reduced by LDL. Preincubation of fibroblasts with HDL (or LDL) reduced the subsequent binding of 1251-LDL (or 125I-HDL) during a second incubation. In other studies HDL reduced the net increase in cell cholesterol content induced by incubation with LDL. HDL alone had no net effect on cell cholesterol content.

“…It is the purpose of this study to extend these findings to man with regard to the following parameters of adipocyte cholesterol: subcellular localization and degree of esterification; effects of cell number, cell size, and plasma cholesterol on adipocyte cholesterol concentration; in vitro cholesterol biosynthetic rates from radioactive glucose and acetate; and compartmental analysis of in vivo adipocyte cholesterol turnover after intravenous infusion of radioactive cholesterol. The last procedure requires the sum of a threeexponential equation to adequately describe cholesterol turnover in man (6,7). By fitting such an equation to both plasma and adipocyte specific activity curves simultaneously, it is possible to compare different threepool models (mammillary and catenary, Fig.…”

mentioning

confidence: 99%

Human adipocyte cholesterol. Concentration, localization, synthesis, and turnover.

Schreibman¹,

Dell²

1975

114

A B S T R A C T By analysis of 124 specimens in 16 different patients, isolated human adipocyte cholesterol concentration is highly correlated with fat cell size but not with plasma cholesterol concentration. Less than 6% of total cholesterol is esterified; after subcellular fractionation, 88% of the cholesterol is recovered in the triglyceride-rich supernatant oil. This latter finding supports the observation that fat cell cholesterol is determined by triglyceride content, and hence by fat cell size.After intravenous administration of radioactive cholesterol, the sum of a three-exponential equation was fit simultaneously to both the plasma and adipocyte specific activity time curves in six patients. In five of the six, a slowly turning over pool (pool 3) closely fit the adipocyte data. Two model structures, mammillary and catenary, were fitted to the data. There was no synthesis in pool 3 using a mammillary model but a mean 5.3% of the total body production rate was found in compartment 3 if a catenary model was assumed. Although a catenary model is biologically unlikely, it could not be excluded.Obesity is associated with an increased cholesterol synthetic rate equal to 20 mg/day for each kilogram of body fat. To test (by an independent method) if this synthesis might be occurring in adipose tissue, human fat cells were obtained under a wide variety of dietary conditions and incubated in vitro with radioactive glucose or acetate. Incorporation of these precursors into sterol could account for no more than 1 mg cholesterol synthesis/kg fat per day. These in vitro data taken togethed with the in vivo mammillary compartmental analysis data are compatible with the possibility that Portions of this work were presented at