Showing papers on "High-density lipoprotein published in 1975"

Role of the low density lipoprotein receptor in regulating the content of free and esterified cholesterol in human fibroblasts.

Abstract: The transfer of normal human fibroblasts from medium containing whole serum to medium devoid of lipoproteins produced a 90 percent decrease in the cellular content of cholesteryl esters and a 30 percent decrease in the free cholesterol content. When these lipoprotein-deprived cells were subsequently incubated with human low density lipoprotein (LDL), there was a 7-fold increase in the cellular content of esterified cholesterol and a 1.6-fold increase in the cellular content of free cholesterol. The concentration at which LDL produced its half-maximal effect in elevating cellular sterol content (30 mug/ml of LDL-cholesterol) was similar to the half-maximal concentration previously reported for high affinity binding of LDL to its cell surface receptor. High density lipoprotein (HDL) and whole serum from a patient with abetalipoproteinemia (neither of which contains a component that binds to the LDL receptor) did not produce a significant increase in the content of either cholesterol or cholesteryl esters in normal cells. Furthermore, in fibroblasts from patients with the homozygous form of familial hypercholesterolemia, which lack functional LDL receptors, LDL had no effect in raising the cellular content of either free or esterified cholesterol even when present in the medium at concentrations as high as 450 mug sterol/ml. It is concluded that LDL-receptor interactions constitute an important biochemical mechanism for the regulation of the cholesterol content of normal human fibroblasts. Moreover, when considered in light of current concepts of LDL metabolism in intact mammals, the present data suggest that a major function of plasma LDL may be to transport cholesterol from its site of synthesis in liver and intestine to its site of uptake in peripheral tissues.

Lipid Metabolism in Pregnancy. III. Altered Lipid Composition in Intermediate, Very Low, Low, and High-Density Lipoprotein Fractions

Abstract: The hyperlipidemia of pregnancy consists primarily of an increase in triglyceride with lesser rises in cholesterol and phospholipid. As a further characterization, we have analyzed all lipids in the major lipoprotein subfractions in fasting pregnant and non-pregnant women. An elevated triglyceride in the major lipoprotein fractions in pregnancy is confirmed. The triglyceride rises in VLDL and IDL (density 1.006-1.019 lipoprotein) are associated with proportional rises in cholesterol and phospholipid. The result is a 3-4-fold increase of compositionally unchanged lipoprotein lipid. Contrasting changes are seen in LDL, density 1.019-1.063 lipoprotein, and HDL. In these fractions, triglyceride rises more than cholesterol and phospholipid. As a result, an increase in triglyceride on a percentage basis tends to reduce the contribution of the other two lipids. Nonetheless, on an absolute basis HDL cholesterol is not significantly reduced. The proportional increases in all lipids of VLDL and IDL fractions are consistent with increased VLDL production in pregnancy as suggested by data from animal systems. However, alterations in removal are not rules out. Maintenance of the HDL cholesterol level distinguishes pregnancy from other endogenous hypertriglyceridemias where HDL cholesterol is reduced. One may speculate that these physiological adaptations in material lipid transport can serve the increased energy needs of the mother, supply steroid hormone precursors for the placenta, and provide cholesterol and essential fatty acids for the fetus.

Lipid profiles of plasma lipoproteins of fasted and fed normal and choline-deficient rats

Abstract: Three major density classes of lipoproteins and a residual protein (d>1.21) were isolated by ultracentrifugation from plasma of fasted, fed normal, and choline-deficient rats. Lipid extracts were obtained from total plasma and the various density classes of lipoproteins, and each extract was examined in detail by thin layer and gas chromatographies. The results indicated essentially identical compositions of molecular species of phosphatidyl choline, which suggested their rapid equilibration among the different plasma lipoprotein classes. In contrast, the molecular species of the triacylglycerols and cholesteryl esters showed significant differences among the chylomicrons, very low and low, and high density lipoproteins, which excluded the possibility of their ready equilibration in vivo. Omission of choline from diet resulted in a sharp and statistically significant decrease in all lipid components of the very low and low density lipoproteins within 2 days. After 10 days of choline deficiency, the lipid levels of chylomicrons and very low and low density lipoproteins were ca. one-half the levels found in the choline supplemented animals, and there were discernible distortions in their lipid composition. Reintroduction of choline led to a prompt return to normal levels and lipid composition of both chylomicron and very low and low density lipoprotein fractions. The lack of equilibration of the triacylglycerols among the lipoprotein classes under normal conditions and in choline deficiency demonstrates an as yet unrecognized source of compartmentation of plasma lipids.

Effects of dietary triglyceride on the properties and lipid composition of plasma lipoproteins: acute experiments in rats fed safflower oil.

Abstract: Male rats were administered 1.5 ml safflower oil by gastric intubation 0, 4, and 8 hr after a 16 hr fast. Plasma, liver, and adipose tissue were collected 16 hr after the last fatty meal. Rats fasted for 16 hr served as controls. Following fat feeding, the fatty acid composition of the very low density lipoprotein, triglyceride, and hepatic triglyceride were similar, as were the percentages of 18:2 in the very low density lipoprotein and hepatic cholesteryl esters. The phospholipids of liver and plasma lipoproteins were similar in the control groups, except that more 16:0 was present in the plasma lipoproteins. After fat feeding, the plasma lipoproein phospholipids were enriched with 18:2 more than were the hepatic phospholipids. Furthermore, the percentage of 18:2 in phospholipid was much less than in triglyceride or cholesteryl esters. Clearly, esterified lipids of liver and plasma lipoproteins (very low density lipoprotein, low density lipoprotein, and high density lipoprotein), and to a lesser extent, adipose tissue, were enriched with 18:2 derived from dietary triglyceride fatty acid even 16 hr after the terminal meal. A major proportion of the very low density lipoprotein isolated by ultracentrifugation in zonal rotors from plasma of fat fed animals had a faster rate-zonal mobility than did the very low density lipoprotein isolated from plasma of control animals. The very low density lipoprotein isolated from plasma of fat fed rats contained fewer moles of phospholipids, cholesterol, and cholesteryl esters, relative to triglyceride than did the very low density lipoprotein from plasma of animals not receiving safflower oil. The molar ratio triglyceride:phospholipid:cholesterol:cholesterol esters in the very low denity lipoprotein was 100:42.0:22.1:44.5 in the control group and 100:35.4:17.8:19.5 in the fat fed animals. It is postulated that an important biochemical mechanism by which dietary triglyceride fatty acids consumed by the animal over a long period of time alter plasma concentrations of triglyceride, phospholipids, and cholesterol esters is the directive influence of plasma free fatty acid, derived from dietary triglyceride, on the secretion of very low density lipoprotein lipids by the liver.

Studies on the inhibitory activities of human serum lipoproteins for Japanese encephalitis virus.

Abstract: Human serum lipoproteins were purified by ultracentrifuging and their concentrations adjusted as required to be within the normal male/female serum range for all assays. The activities in inhibition of hemagglutination (HAI) for Japanese encephalitis virus were--low density lipoprotein (LDL) greater than very low density lipoprotein (VLDL) greater than high density lipoprotein (HDL). Heating (56 degrees C/30 minutes) caused the LDL titer to fall and freeze-thawing (20 degrees C/room temperature) the VLDL titer to rise slightly, possibly as a result of alteration in lipoprotein structure. The additon of lipoprotein depleted serum appeared to dampen these effects and there was no nett change in titer when it was added to a lipoprotein mixture. Similarly, unfractionated normal serum showed no significant change in titer after these treatments. The lipoproteins lacked significant virus neutralizing (VN) activity and this remained so in spite of fluctuations in HAI titer after heating and freeze-thawing.

The distribution of J blood-group activity on lipoprotein and protein fractions of bovine serum.

Abstract: There is a diversity of carriers of the J blood-group activity of bovine serum. The qualitative and quantitative distribution of the J activity on different carriers was studied, using various fractionation procedures. Approximately one third of J activity was found in the total lipids extracted from serum, two thirds in the lipid-free residue precipitated by lipid extraction. One third of the lipid J substance was found to be bound to the very low density lipoprotein, two thirds to the low density lipoprotein, while the high density lipoprotein was completely free of J activity. All non-lipidic J substance was present in the lipid-free protein. There was no J activity in the low molecular weight mucoproteins of serum and in the apoproteins of the lipoprotein fractions. The lipoprotein fractions were prepared by ultracentrifugation at different solvent densities. The lipoprotein fractions were characterized by chemical analyses and physical properties. The lower total cholesterol concentration of bovine serum, as compared to human serum, is reflected in a lower concentration of low density lipoprotein. The results obtained by ultracentrifugation coincide with the results obtained by precipitation of “β-lipoproteins” with dextran sulfate and calcium chloride and with results obtained by gel filtration of bovine serum. The “β-lipoprotein” fraction contains lipoproteins of very low and low density, and probably chylomicrons and a variety of other proteins, however no high density lipoprotein.

Development of hyperbetalipoproteinemia in pigs fed atherogenic diet.

Abstract: Hormel miniature pigs were studied over a period of 24 weeks to observe the changes in serum lipoprotein pattern, cholesteryl ester, free cholesterol, and triglyceride in the atherogenic-fed pigs. These pigs were compared to age-related control animals in our breeding herd. Pigs fed the atherogenic diet (20% tallow, 3% cholesterol, and a bile supplement) exhibited a heterogeneous response but showed mean increases in cholesteryl ester (571 mg/dl) and free cholesterol (226 mg/dl), a slight increase in triglyceride (58 mg/dl), and a severe hyperbetalipo proteinemia. Three animals with the highest cholesteryl ester (all above 600 mg/dl) had resolvable β components in their 1.006 g/ml very low density lipoprotein fraction (type III), as well as huge increases in the Sf 12–20 low density lipoprotein fraction. The other four animals had substantial increases in Sf 0–20, and the three highest had much of their low density lipoprotein in the Sf 12–20, or “remnant” fraction. The test pigs all showed gross lesions in the aorta with an increase in cholesteryl ester and free cholesterol in the tissue as compared with control animals.

Steroid requirements for suppression of HMG CoA reductase activity in cultured human fibroblasts.

Abstract: The rate of cholesterol synthesis in cultured human fibroblasts is determined by the activity of 3-hydroxy-3-methylglutary1 coenzyme A reductase (HMG CoA reductase) (1–3). The activity of this enzyme in normal fibroblasts becomes suppressed when low density lipoproteins (LDL) bind to specific receptors on the cell surface (4, 5) and deliver cholesterol and cholesteryl esters to the cell (6). High density lipoproteins (HDL), which do not bind to the LDL receptor (4, 5), do not increase the cellular content of cholesterol and cholesteryl esters (6) nor do they suppress HMG CoA reductase activity and cholesterol synthesis (1, 3). Cultured fibroblasts from subjects with the autosomal dominant disorder familial hypercholesterolemia are deficient in the LDL receptor (4, 5, 7). As a result, LDL does not bind to the cells (4, 5, 7), cholesterol is not transferred intracellularly (6), HMG CoA reductase activity is not suppressed, and cholesterol is overproduced (2, 3).

Cholesterol Metabolism in Man

Abstract: Cholesterol is an important structural component of all cellular and intracellular membranes as well as of plasma lipoproteins. The cholesterol present in plasma is only a small fraction of the total present in the body but is, in many respects, the most important fraction. Patients with hypercholesterolemia have a greater risk of developing atherosclerosis of the coronary arteries. Conversely, reduction in plasma cholesterol may reduce the risk of death from myocardial infarction. Elevation of plasma cholesterol is assumed to increase the rate of deposition of cholesterol in tissues, including the arterial intima: the site of atherosclerotic lesions. The pathological effects of total circulating cholesterol may be significantly modified by the differences in the spectra of plasma lipoproteins. Attempts to decrease plasma cholesterol by diet or drugs are based on the hope that reduction in the rate of deposition of cholesterol may retard the development of lesions and also the risk of myocardial infarction.