Very Low Density Lipoprotein Lipids Research Articles

Regulation of hepatic very-low-density lipoprotein secretion in rats fed on a diet high in unsaturated fat.

Rats were fed ad libitum on either a standard, high-carbohydrate, chow diet or a similar diet supplemented with 15% unsaturated fat (corn oil). Hepatocytes were prepared either during the dark phase (D6-hepatocytes) or during the light phase (L2-hepatocytes) of the diurnal cycle. In hepatocytes from rats fed on the unsaturated-fat-containing diet, secretion of very-low-density lipoprotein (VLDL) triacylglycerol was inhibited to a greater extent in the D6- than in the L2-hepatocytes. Plasma non-esterified fatty acid concentrations were elevated to the same extent at both D6 and L2 in the unsaturated-fat-fed animals. The secretion of VLDL esterified and non-esterified cholesterol was relatively insensitive to changes in the unsaturated-fat content of the diet. This resulted in proportionate increases in the content of these lipid constituents compared with that of triacylglycerol in the nascent VLDL. There was also an increase in the ratio of esterified to non-esterified cholesterol in the nascent VLDL produced by hepatocytes of the unsaturated-fat-fed animals. In the D6-hepatocytes from the unsaturated-fat-fed animals, the decrease in the secretion of VLDL triacylglycerol could not be reversed by addition of exogenous oleate (0.7 mM) to the incubation medium. In contrast, addition of a mixture of lactate (10 mM) and pyruvate (1 mM) stimulated both fatty acid synthesis de novo and the rate of VLDL triacylglycerol secretion. Secretion of esterified and non-esterified cholesterol also increased under these conditions. Insulin suppressed the secretion of VLDL triacylglycerol and cholesteryl ester under a wide range of conditions in all types of hepatocyte preparations. Non-esterified cholesterol secretion was unaffected. In hepatocytes prepared from the fat-fed animals, these effects of insulin were more pronounced at D6 than at L2. Glucagon also inhibited VLDL lipid secretion in all types of hepatocyte preparations. The decrease in cholesterol secretion was due equally to decreases in the rates of secretion of both esterified and non-esterified cholesterol.

Very low density lipoproteins (VLDL) trigger the release of histamine from human basophils

Circulating basophils are well established sources of the granule-associated mediator, histamine. The physiological control, however, of histamine release from human basophils is poorly understood. Because histamine may play a role in the transendothelial transport of various compounds, including very low density lipoprotein (VLDL) and its hydrolysis products, we investigated the possibility that VLDL regulates mediator release from basophils. The incubation of VLDL (at physiological concentrations) with basophils (isolated as mixed leukocyte preparations) resulted in a significant release of histamine. Histamine release was dependent on VLDL concentration (half-maximal stimulation occurring at VLDL-protein concentration of 15-20 micrograms/ml), length of incubation (half-maximal release at 5-12 min), temperature (37 degrees C optimum) and required calcium (concentration 0.5-2.0 mM). Furthermore, VLDL-induced histamine release was inhibited by three different mediator-release inhibitors: dimaprit, dibutyryl cAMP and nordihydroguaiaretic acid. Incubation of basophils with LDL or HDL under the same experimental conditions did not result in significant histamine release from basophils. The histamine-secretory response of basophils obtained from different donors varied considerably. Basophils isolated from 28 donors and challenged with 100 micrograms/ml VLDL released 23 +/- 5% of their cellular histamine (mean +/- S.E.; with a range of 0-94%). Desensitization of VLDL-induced histamine release could be accomplished by preincubation of basophils with either VLDL or anti-IgE but not with N-formyl-L-methionyl-L-leucyl-L-phenylalanine. Through the secretion of histamine, a potent vasoactive mediator (and also possibly through granule-associated glycosaminoglycans, stimulants of the enzyme lipoprotein lipase), this novel effect of VLDL may be part of a physiological loop for the regulation of VLDL hydrolysis and lipid transport. This effect of VLDL may also have deleterious consequences, because of the atherogenic properties of histamine.

Relationship of angiographically defined coronary artery disease to serum lipoproteins and apolipoproteins in young survivors of myocardial infarction.

The relationship of serum lipoprotein and apolipoprotein concentrations to angiographically determined coronary artery disease was investigated in 105 consecutive male survivors of myocardial infarction under the age of 45. Concentrations and composition of lipoproteins, lipid indexes, and nonlipid risk factors (tobacco consumption, hypertension, reduced glucose tolerance, and obesity) were related to a recently developed scoring system for semiquantitative estimation of diffuse coronary atheromatosis, as well as to the number and severity of significant coronary artery stenoses. The concentrations of cholesterol in very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), in combination with serum triglyceride or VLDL triglyceride level, comprised the best set of independent discriminatory lipid variables between patients and control subjects. In the patients, LDL cholesterol and apolipoprotein B levels showed strong relationships to the extent and severity of coronary atheromatosis but not to the number and severity of distinct coronary stenoses. HDL2 cholesterol concentration correlated inversely with the coronary atheromatosis score, whereas other variables reflecting HDL concentration and composition or VLDL lipids were not independently related to any of the coronary scores. The LDL triglyceride level, an index of intermediate-density lipoprotein (IDL) accumulation, was significantly correlated to the coronary atheromatosis score in univariate analysis. Nonlipid risk factors were correlated neither to coronary atheromatosis nor to severity of stenoses. Stepwise multiple regression analyses of data adjusted for age, cumulative tobacco consumption, and weight indicated that 18% of the variation in the coronary atheromatosis score could be accounted for by levels of apolipoprotein B. Addition of other lipoprotein variables or the nonlipid variables hypertension and glucose tolerance did not significantly increase the value of R2. When ratios of lipoprotein lipids and apolipoproteins were included in the regression model, the highest multiple correlation coefficient was obtained with the LDL/HDL cholesterol ratio alone (R2 = .22). The present data demonstrate the importance of elevated LDL cholesterol and apolipoprotein B concentrations for the development of coronary atheromatosis in young male survivors of myocardial infarction. The lack of correlations between the levels of lipoprotein lipids and serum apolipoproteins and the severity of coronary stenoses suggests that mechanisms other than disturbances of lipoprotein metabolism may be involved in the progression of more advanced coronary lesions.

Acute inhibition of hepatic lipase and increase in plasma lipoproteins after alcohol intake.

Chronic alcohol intake is associated with an increase in fasting plasma high density lipoproteins (HDL). To study alcohol's acute effects on plasma lipoproteins, we measured plasma lipoprotein concentrations and activities of postheparin plasma lipases in nine normolipemic males after ingestion of 40 g of ethanol (as whiskey). After alcohol there was no change in lipoprotein lipase activity but hepatic lipase was decreased to 67% of baseline at 6 hr. There were associated increases in HDL phospholipids (12 mg/dl) and cholesterol (10 mg/dl) resulting in prominence of larger, lipid-enriched HDL particles. Changes were most pronounced in the HDL3 and HDL2a subclasses. Very low density lipoprotein (VLDL) phospholipids and cholesterol were also increased by 13 and 9 mg/dl, respectively, with no significant change in triglycerides. Changes in lipoproteins and lipase were largely reversed 10 hr after alcohol intake. The transient increases in VLDL and HDL lipids after alcohol may result in part from acute inhibition of hepatic lipase activity. The results suggest a role of hepatic lipase in the catabolism of phospholipids of VLDL and possibly HDL.

Turnover of very low-density lipoprotein-apoprotein B is increased by substitution of soybean protein for meat and dairy protein in the diets of hypercholesterolemic men

The effect of dietary protein source on the kinetics of plasma very low-density lipoprotein (VLDL) (Sf 60 to 400) in hypercholesterolemic men was investigated. Using a crossover design, five subjects received sequentially either 1) a high polyunsaturated fat, low cholesterol control diet containing mixed protein from meat, dairy products, and plant sources or 2) an all-plant protein experimental diet in which the meat and dairy protein of the former diet was replaced by soybean protein and soy milk. There was no significant change in the mean values for fasting serum cholesterol and triglycerides over the 6-wk period of administration of the control versus experimental diets. The kinetics of VLDL (Sf 60 to 400) apolipoprotein B were studied at the end of each dietary period after reinjection of 125I-labeled autologous VLDL (Sf 60 to 400). The VLDL apolipoprotein B pool size was similar during the experimental and control protocols; however, the fractional catabolic rate was consistently higher during the experimental protocol (8.5 ± 1.3 versus 6.5 ± 1.2 day−1, p < 0.01) and the production rate of apoprotein B was higher than control in four of five subjects (mean values 18.6 ± 3 versus 12.6 ± 1 mg/day/kg, respectively). Administration of an all-plant protein diet significantly increased the fractional turnover rate of VLDL apolipoprotein B, even when no changes in VLDL apo B pool size or VLDL lipid concentrations were observed.

Lipid metabolism in nephrotic rats induced by daunomycin injection

Lipid metabolism in the blood and liver of rats was investigated to clarify the mechanism of dyslipoproteinemia in the nephrotic syndrome. The nephrotic syndrome was induced in rats by a single injection of daunomycin. The serum total cholesterol, triglyceride, and phospholipid levels in nephrotic rats 14 days after the injection were increased 3.1-fold, 2-fold, and 2.7-fold, respectively, over the control values. The cholesterol, triglyceride, and phospholipid contents of high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) were also increased, increase in VLDL lipids being the greatest. The serum HDL cholesterol level decreased gradually after day 14, returning to the normal level on day 37, whereas the LDL and VLDL cholesterol levels continued to increase until day 37. The mechanism of dyslipoproteinemia in the nephrotic syndrome was examined by comparing lipid metabolism in the liver of nephrotic rats induced by daunomycin with that of rats fed on high-cholesterol diet. The contents of total lipids, triglyceride, and cholesterol ester in the liver were significantly less in nephrotic rats than in controls. The contents of total lipids and cholesterol ester in the liver were much higher in rats fed on high-cholesterol diet than in controls. The contents of total lipids, triglyceride, cholesterol ester, and phospholipid in the liver were significantly lower in nephrotic rats fed on high-cholesterol diet than in normal rats fed on high-cholesterol diet. [1- 14C]Acetate incorporation into liver lipids was higher in nephrotic rats and lower in rats fed on high-cholesterol diet than in controls. [1- 14C]Palmitate incorporation into liver lipids was higher in nephrotic rats and rats fed on high-cholesterol diet than in controls. These data suggest that discharge of lipids, de novo synthesis of lipids, and utilization of preformed free fatty acids were all stimulated in the liver of rats with the nephrotic syndrome induced by daunomycin. However, although the utilization of preformed free fatty acids was stimulated, de novo synthesis of lipids was suppressed in the liver of rats fed on high-cholesterol diet.

Dose-response study of the effect of ciprofibrate on serum lipoprotein concentrations in hyperlipoproteinaemia

The effect of ciprofibrate, 2[ p-(2,2-dichlorocyclopropyl)-phenoxyl]-2-methyl propionic acid, in daily doses of 50, 100 and 200 mg was studied in 50 patients with hyperlipoproteinaemia (21 type IIA, 10 type IIB and 19 type IV). Ciprofibrate was convenient to take and was without subjective side effects. The greatest hypolipidaemic effects were reached for all lipoproteins with 200 mg daily. In type IIA and IIB, mean low density lipoprotein (LDL) cholesterol was normalized on the 200 mg dose. The effect was highly dependent on initial LDL cholesterol concentrations, decreases being observed above 4 mmol/1 and increases below that concentration. Mean very low density lipoprotein (VLDL) triglyceride concentrations decreased on 200 mg per day by 48–59%. HDL cholesterol increased in all types of hyperlipoproteinaemia by 6–19%, the change being unrelated to changes in VLDL lipids. With a dosage of 200 mg daily the effects were maintained for the following period of 6 months. It is concluded from this study that it would be appropriate to start patients on 100 mg daily and then titrate their dose according to response. The optimal dosage for ciprofibrate seems to be 200 mg daily.

Effects of bezafibrate on the composition of very low density lipoproteins in type IV hyperlipoproteinemia

As compared to normolipoproteinemic controls 10 male subjects with primary type IV hyperlipoproteinemia had higher apolipoprotein E and lower apolipoprotein C-II concentrations in the very low density lipoprotein (VLDL) fraction. After 8 weeks of treatment with 0.6. g/day bezafibrate, cholesterol and triglyceride in the serum and VLDL were significantly lower. The decrease of VLDL lipids was accompanied by a significant decrease of the apolipoproteins and of the lipid/protein ratio in VLDL. The analysis of the soluble VLDL apolipoproteins revealed a decrease of apo E and an increase of apo C1 and apo C2, resulting in a decrease of the apo E/apo C ratio.

Viscosity of culture medium as a regulator of synthesis and secretion of very low density lipoproteins by cultured hepatocytes.

It has been postulated that hyperlipidemia in the nephrotic syndrome is due to overproduction of lipoproteins and that low colloid osmotic pressure (due to hypoalbuminemia) triggers this. Secretion of very low density lipoproteins (VLDL) by cultured rat hepatocytes has been shown to be inhibited by albumin, globulins, and dextrans, but the effect did not correlate with osmolarity. In the present studies we tested the hypothesis that viscosity rather than osmolarity might be the parameter determining the effectiveness of macromolecules in inhibiting VLDL synthesis and secretion by cultured rat hepatocytes. Synthesis and secretion of VLDL was measured in terms of incorporation of [3H] glycerol into medium triglycerides and also from changes in the mass of secreted VLDL triglycerides and apoproteins. The viscosity of the culture medium was increased by addition of dextran-500, gelatin or methylcellulose MX 880. Synthesis and secretion of VLDL was inhibited in direct proportion to increasing viscosity. At a viscosity of 2, which is about that of normal plasma, VLDL secretion was reduced by 20%. An inhibition of 60-70% in secretion and 30-40% in synthesis of VLDL lipid and protein components was observed at a relative viscosity of approximately 3.7. This viscosity was obtained by addition of any of the following: 3% dextran, 3% gelatin, 0.2% methylcellulose, or a combination of 0.1% methylcellulose plus 2% gelatin. Thus, similar viscosities resulted in similar degrees of inhibition despite differences of up to 16-fold in mass concentration and up to 20-fold in osmolarity.

Lack of induction of VLDL apoprotein synthesis by medium chain fatty acids in the isolated rat liver.

Long chain fatty acids (greater than C16) are known to induce the liver synthesis of very low density lipoprotein (VLDL) apoproteins. Since medium chain (less than C16) triglycerides are used as dietary fats and in parenteral nutrition, we have investigated the relative uptake, esterification and oxidation of 14C-labelled fatty acids of a chain length of C10-C14 by the perfused rat liver compared to palmitic acid at two different concentrations: tracer (control) and overload (200 or 600 mumol/200 ml perfusate). The effect on VLDL apoprotein synthesis was simultaneously estimated by 3H-leucine incorporation. The results show: (1) a rapid liver uptake of all fatty acids; (2) a substantial incorporation into liver lipids of C12-C14 and C16, and (3) a higher oxidation rate of medium chain compared to long chain fatty acids; a lack of induction of VLDL apolipoprotein by an overload of fatty acids shorter than palmitic acid in spite of their utilisation for liver and VLDL lipid synthesis. Possible explanations for these differences are discussed.

Differential scanning calorimetry and fluorescence probe investigations of very low density lipoprotein from the isolated perfused rat liver.

Isolated rat livers were perfused at 37 degrees C with blood-free, defined medium containing delipidized bovine serum albumin (BSA), BSA-oleate, or BSA-palmitate. Very low density lipoproteins (VLDL) were isolated from the perfusate at 12 degrees C and lipid components were extracted and purified. Differential scanning calorimetry indicated multiple phase alterations in intact VLDL. The extracted triglycerides exhibited phase alterations at similar temperatures as the intact VLDL. The small quantities of cholesteryl esters present in the VLDL generally did not greatly affect the VLDL triglyceride transitions. The extracted phospholipids showed detectable transitions that were abolished by cholesterol at mole ratios found in the respective VLDL. The phase behavior of VLDL and its component triglycerides was associated with the degree of unsaturation of the infusate fatty acid, and by variation of fatty acid chain length. The structural differences between VLDL lipid fractions noted by DSC were also monitored by fluorescence probes. The data indicated that in the intact VLDL the physical properties of the 'interior core' lipids can affect the properties of the 'surface monolayer'. In addition, Arrhenius plots of corrected fluorescence indicated that trans-parinarate and diphenyl-hexatriene detected different characteristic breakpoint temperatures in the phospholipids. The breakpoints of triglycerides were highly dependent on the type of fatty acid in the infusate, but were similar to those noted in intact VLDL. Finally, the breakpoints in Arrhenius plots of fluorescence probe parameters did not necessarily coincide with onset or end temperatures of DSC transitions.

Composition of plasma and nascent very low density lipoprotein from perfused livers of hypercholesterolemic squirrel monkeys.

The composition of circulating very low density lipoprotein (VLDL) was compared with the composition and secretion of nascent VLDL from perfused livers of squirrel monkeys that were fed unsaturated or saturated fat diets to elicit different degrees of plasma hypercholesterolemia. All squirrel monkeys studied had cholesteryl ester-rich plasma VLDL, although greater enrichment occurred in hypercholesterolemic animals fed saturated fat. Livers from hypercholesterolemic animals were capable of secreting VLDL particles enriched in cholesteryl ester, suggesting hepatic origin for a portion of this circulating lipid moiety. Total VLDL lipid, but not protein output by perfused livers of hypercholesterolemic monkeys, was greater than that by livers from hypocholesterolemic animals. These results indicate that saturated fat-induced hypercholesterolemia is associated with changes in the composition of hepatic VLDL in the squirrel monkey.

Intestinal Secretion of Lipids and Lipoproteins during Carbohydrate Absorption in the Rat

To assess the effects of carbohydrate ingestion on the characteristics and quantities of triglyceride-rich lipoproteins produced by the intestine, mesenteric lymph was collected from rats receiving intraduodenal infusions of saline, sucrose or starch. Lymph total lipid (mg/hour) was greatest during saline infusion, decreased during sucrose and became significantly less (P less than 0.05) during starch infusion. Lipoproteins were isolated from lymph by ultracentrifugation followed by gel filtration chromatography. During saline infusion total lipid in very low density lipoproteins (VLDL) was 2-fold higher than total lipid in chylomicrons; with both carbohydrate infusions this ratio increased to seven. Both carbohydrates significantly lowered the rate of secretion of total lipid as chylomicrons. The VLDL lipid secretion rates during sucrose infusion were equivalent to those during saline, whereas starch infusion tended to decrease VLDL lipid secretion rates. These results suggest that during the process of carbohydrate absorption, carbohydrate does not enhance the flow of intestinal VLDL into the circulation; digestion and absorption of complex carbohydrates in fact may retard the intestinal contribution of triglyceride-rich lipoproteins.

Lipolysis Produces Changes in the Immunoreactivity and Cell Reactivity of Very Low Density Lipoproteins

Smaller very low density lipoprotein (VLDL) remnants interact more readily with tissues than do larger "intact" VLDL. This may be related to changes in the availability of VLDL apoproteins on the surface of the lipoproteins. To test this hypothesis VLDL were incubated at 37 degrees C with bovine milk lipase (LPL), and the abilities of LPL-treated VLDL preparations to compete with (125)I-low density lipoproteins (LDL) for interaction with cultured normal human fibroblasts were measured. At the same time, the immunologic activities of these preparations were also tested by double antibody radioimmunoassay. Triglyceride (TG) contents of VLDL fell by 30-90% during incubation with LPL and, on zonal ultracentrifugation, VLDL of faster Svedberg unit of flotation (S(f1.063)) rates (>150) were gradually converted to smaller VLDL with lower S(f) rates (21-60). LPL-treated VLDL competed two to five times more effectively with (125)I-LDL for binding to cellular receptors than did control VLDL. Control VLDL incubated with heat-inactivated LPL at 37 degrees C, or with active LPL at 4 degrees C had unaltered cell reactivities and TG contents compared with VLDL incubated without any enzyme. The direct uptake and degradation of LPL-treated VLDL was also assessed by using VLDL (125)I-labeled in apoprotein (Apo)B. LPL-treated VLDL-(125)I-ApoB were taken up and degraded by fibroblast at greater rates than were control VLDL-(125)I-ApoB. Thus, hydrolysis of VLDL lipids was accompanied by an increased ability of VLDL to interact with fibroblasts. The immunoreactivity of ApoB in the same VLDL preparations, expressed as the "apparent ApoB contents" of LPL-treated VLDL, increased by 10-50% (P < 0.02) in those assays that contained anti-LDL antisera, but the ApoB of control VLDL remained constant. However, assays that contained antisera directed against ApoB isolated from VLDL did not distinguish between LPL-treated and control VLDL. Thus, VLDL lipid hydrolysis was accompanied by changes in the immunoreactivity of VLDL-ApoB, which probably reflect changes in the disposition of ApoB on the surface of VLDL. The altered disposition of ApoB on VLDL "remnants" may be related to their enhanced interaction with cells.

Comparative studies of the physical state of the lipid phase of normal and hypercholesterolemic very low density lipoprotein

Very low density lipoproteins (VLDL) were prepared from the serum of rabbits at various stages of hypercholesterolemia (95–1665 mg cholesterol/100 ml of serum). The most notable chemical change in hypercholesterolemic (hc) VLDL was the greatly increased content of cholesteryl esters and the greatly decreased content of triglycerides, compared to normal (n) VLDL. Structurally, the lipid region of n VLDL possessed a much lower microviscosity than did hc VLDL, when analyzed by fluorescence polarization and pyrene eximer methods. The microviscosity of the redispersed n VLDL lipid extract was considerably greater than that observed in n VLDL; but less than that of hc VLDL. Incorporation of pyrene into the lipid region of n VLDL and hc VLDL allowed assessment of various properties of the surface and hydrocarbon regions of these lipoproteins. Only slight differences were found in the pyrene monomer 3 : 1 fluorescence emission peak ratios, and in the rate constant for quenching of pyrene by O 2. However, the quenching rate constant of pyrene by I − and iodoheptane were different for each lipoprotein.

The effect of a low-cholesterol, high-polyunsaturate diet on serum lipid levels, apolipoprotein B levels and triglyceride fatty acid composition

1. (1) Seven healthy normolipaemic men aged 28–46 years (mean 33 years) were studied for four weeks on their usual diet, the mean polyunsaturated to saturated fat (P : S) ratio of which was approximately 0.23 and the cholesterol content 667 mg/day, and for four weeks on an isocaloric diet, containing similar proportions of protein, carbohydrate and fat, but with a mean P : S ratio of approximately 2.82 and a cholesterol content of 112 mg/day. 2. (2) Total serum cholesterol levels decreased by 18.7 ± 5.2% (mean ± SEM) on the polyunsaturated fat (PUF) diet. This was attributable to a similar reduction in serum low density lipoprotein (LDL) cholesterol. Serum very low density lipoprotein (VLDL) cholesterol showed no clear change. Total serum triglyceride levels decreased by 19.7 ± 7.1% due to a reduction in both serum VLDL and LDL triglyceride concentration. 3. (3) Total serum apolipoprotein B concentration fell by 23 ± 2.6% during the PUF diet. There was a decrease of similar magnitude in serum LDL apolipoprotein B, but no sustained effect on serum VLDL apolipoprotein B. 4. (4) Serum VLDL and LDL lipid to apolipoprotein B ratios did not change significantly during the study. 5. (5) Serum triglyceride fatty acid composition significantly altered during the PUF diet. The percentage of linoleic acid rose from 16 ± 0.90% to 36 ± 0.89%, whilst the percentage of combined saturated and monounsaturated acids fell correspondingly. These changes took place within 2 days of starting the PUF diet.

The effect of a short term saturated fat diet on the apoprotein composition and radioiodination properties of rat very low density lipoproteins

The effect of a saturated fat diet on the apoprotein composition and radioiodination properties of plasma very low density lipoprotein (VLDL) was studied in rats. After feeding the diet for 10 days, the proportion of 125I attached to VLDL lipid decreased from 50% (control animals) to 8%, the remainder (92%) being bound to the apoprotein components. The decreased lipid labelling was associated with proportional changes in the fatty acid composition of serum and VLDL lipids, the most notable change being a reduction in linoleic acid (30-8%) content which occurred in all the major lipid classes of both serum and VLDL. Analysis of VLDL after radioiodination showed that most of the radioactivity incorporated into the lipid moiety was associated with phospholipid. The proportion of 125I bound to phospholipid decreased after feeding rats a saturated diet. The proportion of soluble (small molecular weight peptides and arginine rich peptide) to insoluble (B apoprotein) did not alter during the saturated fatty acid dietary regime and no differences in the distribution of soluble proteins were observed. It is concluded that feeding a saturated fat diet to rats for 10 days significantly improved 125I labelling of the apoprotein moiety while apparently not inducing changes in apoprotein composition.

Effects of sex on formation and properties of plasma very low density lipoprotein in vivo

The concentration and composition of the very low density lipoprotein (VLDL) lipids and the behavior of the VLDL in a density gradient in the zonal ultracentrifuge were examined in plasma obtained from normal fed male and female rats before and after intravenous injection of Triton WR-1339. Concentration of lipids in plasma VLDL of female rats was about half that of male animals. Following injection with Triton WR-1339, the concentration of VLDL lipids was higher in female rats (triacylglycerol) or similar (phospholipid, cholesterol, and cholesteryl esters) in both sexes. Female rats secreted much more VLDL traicylglycerol into the plasma compartment than did the male animals under the same experimental conditions. No differences were observed in lipid composition of the VLDL or in the position of the VLDL in the zonal rotor after ultracentrifugation in a density gradient of the lipoprotein from plasma of normal male and female rats before treatment with the detergent. However, after treatment with Triton, a higher proportion of the VLDL particles isolated from plasma of female rats displayed a more rapid rate-zonal flotation in the ultracentrifuge than did the VLDL produced by the male. The VLDL secreted by female rats contained fewer moles of phospholipid and free sterol per mol triacylglycerol than did the VLDL secreted by male animals under identical experimental conditions. The molar ratio of free cholesterol:cholesteryl ester in the VLDL secreted after treatment with Trition increased in both male and female rats. Simultaneously, the content of arachidonic acid in phospholipid of VLDL increased with a concomitant decrease in cholesteryl ester. These changes in fatty acid composition suggest that the inhibitory effect of Triton on lecithin-cholesterol acyl transferase activity affects the exchange of lipids between VLDL and high density lipoprotein. It can be concluded from the data reported here that sex influences the concentration of plasma lipids in vivo and the output and properties of the VLDL.

Lipoprotein Composition and Lipoprotein Interrelations in 50-year-old Men with Hyperlipoproteinaemia

The serum lipoprotein (LP) composition and LP lipid interrelations were studied in 50-year-old men with different types of hyperlipoproteinaemia (HLP) and in randomly sampled health controls from the same population. The ratio cholesterol/triglycerides in very low density lipoproteins (VLDL)was high in HLP type III. The other types of HLP showed ratios not significantly different from the controls. The low density lipoprotein (LDL) cholesterol concentration was similar in controls, type III and type IV while, by definition, higher values were seen in type II A and II B. All types of HLP showed statistically significantly higher LDL triglycerides than the controls. HLP type II A and II B showed cholesterol/triglyceride ratios in LDL similar to the controls. The corresponding ratio in type IV was lower than in the control subjects but the lowest ratio was seen in type III with a mean value below the 5th percentile of healthy controls. The high density lipoprotein (HDL) cholesterol concentration was decreased in HLP type IV. Apparently elevated HDL triglyceride levels were seen in all types of HLP with the highest mean value in type III. The LP lipid interclass relationships were analysed in the random sample of health men and compared to corresponding relationships in the different types of HLP. Apart from HLP type III and HLP type IV with low LDL cholesterol levels all other types of LP interconversions. Intype IV a significant negative correlation between VLDL concentration and LDL cholesterol concentration and the cholesterol/triglyceride ratio in VLDL. There were no significant correlations between LDL cholesterol concentration and VLDL lipid variables in other types of HLP and normolipidaemia.