The composition and metabolism of high density lipoprotein subfractions

The composition and metabolism of high density lipoprotein (HDL) subfractions were investigated in seven nomal individuals. Mean HDL₂ (d, 1.063–1.125 g/ml) composition (by weight) was 43% protein, 28% phospholipid, 23% cholesterol, and 6% triglyceride, and mean HDL₃ (d, 1.125–1.21 g/ml) composition was 58% protein, 22% phospholipid, 14% cholesterol, and 5% triglyceride. The mean apoA-I; apoA-II weight ratio was 4.75 for HDL₂ and 3.65 for HDL₃.HDL₂ protein was proportionally slightly richer in C apolipoproteins and higher molecular weight constituents (including apoE) than HDL₃. Kinetic studies utilizing radiolabeled HDL_A (d, 1.09–1.21 g/ml), HDL₂, and HDL₃ demonstrated rapid exchange of apoA-I and apoA-II radioactivity among HDL subfractions, similar fractional rates of catabolism of apoA-I and apoA-II within HDL, and similar radioactivity decay within HDL subfractions. Mean plasma residence time was 5.74 days for radiolabeled HDL₂ and 5.70 days for radiolabeled HDL₃. Differences in HDL protein mass among individuals were largely due to alterations in catabolism, and in general both HDL₂ and HDL₃ were catabolized via a plasma and a nonplasma pathway. Data from simultaneous radiolabeled very low density lipoprotein and HDL studies in 2 individuals are consistent with the concept that apoC-II and apoC-III are catabolized at a different rate than are apoA-I and apoA-II within the HDL density range.     

The distribution of serum high density lipoprotein subfractions in non-human primates

The ultracentrifugal flotation patterns in 1.2 g/ml solvent and ultracentrifugal gradient distribution of high density lipoproteins (HDL) from the primates-human, apes and monkeys-were determined, with emphasis on the gorilla species of apes and rhesus monkeys. Diets for non-human primates were commercial chow, which is low in cholesterol. Molecular weights and protein, cholesterol, phospholipid and triglyceride compositions of various density fractions were determined on human, gorilla and rhesus HDL. The HDL₂/HDL₃ ratio was determined from the two peaks observed upon flotation in high salt in the analytical ultracentrifuge. The HDL₂ of all three species of apes-gorillas (Gorilla gorilla), chimpanzees (Pan troglodytes) and orangutans (Pongo pygmaeus)—was always greater than HDL₃, while that of all six species of Old World monkeys-Rhesus (Macaca mulatta), sooty mangabeys (Cercocebus atys), cynomolgus (Macaca fascicularis), stumptails, (Macaca arctoides) patas (Erythrocebus patas) and African greens (Cercopithecus aethiops)—was less. In addition, the HDL₃ concentration in five gorillas was about 15 mg/dl as cholesterol while the HDL₂ concentration was 92 mg/dl, much lower and higher, respectively, than humans. HDL₂ of gorillas was similar in density and molecular weight to that of humans. The distribution of densities in gorilla HDL was predominantly in HDL₂, while rhesus HDL usually, but not always, was unimodal, having a density distribution similar in heterogeneity to human HDL₃, but somewhat less dense (peaking at 1.109 vs 1.129 g/ml). The molecular weight of rhesus HDL was about the same as human HDL₃ in all three density subfractions and at the peak density. Likewise, the chemical compositions were similar for the subfractions 1.10–1.125 and>1.125 g/ml for rhesus HDL and human HDL₃. Consequently most but not all chow-fed rhesus HDL was very similar to human HDL₃, but lighter in density. A preliminary report of this study was given at the American Society for Biological Chemists Meeting in New Oreleans in April 1982.     

Sedimentation equilibrium of human low density lipoprotein subfractions

The molecular weights of low density lipoprotein (LDL) subfractions were determined precisely by meniscus depletion sedimentation equilibrium. Equilibrium speeds ranged from 9743 to 5896 rpm. The average molecular weights of various LDL subfractions of S_f ^o values 9.49, 7.94, 6.42, 5.17, and 3.71 determined by sedimentation equilibrium were 2.97×10⁶; 3.13×10⁶; 2.89×10⁶; 2.45 ×10⁶; and 2.61×10⁶ daltons, respectively; and their respective densities were 1.0267, 1.0306, 1.0358, 1.0422, and 1.0492 g/ml. Minimal hydrated molecular weights for these fractions determined by flotation velocity at 37,020 rpm were 2.57×10⁶; 2.37×10⁶; 2.09×10⁶; 1.94×10⁶; and 1.81 ×10⁶ daltons; whereas similar molecular weights determined at 52,640 rpm were 2.53×10⁶; 2.27 ×10⁶; 1.99×10⁶; 1.86×10⁶; and 1.74×10⁶ daltons for the respective LDL subfractions. Higher molecular weights of fractions 2 and 5 compared to their adjacent fractions 1 and 4 by sedimentation equilibrium are of great interest. The calculated frictional ratio f/f^o from sedimentation equilibrium and flotation velocity data ranges from 1.10 to 1.31, suggesting complexity and asymmetry of LDL subfraction molecules. There is also evidence that compressibility of LDL molecules may be different than that for the salt solution under high g-force. Assuming that redistributed LDL molecules at equilibrium under low g-force are spherical, it is possible that the shape of LDL molecules undergoing flotation velocity determinations may be distorted in high g-force conditions. Such distortion may be consistent with the high f/f^o values obtained and may also be a basis for structural rearrangement and/or lipoprotein degradation with prolonged preparative ultracentrifugation at high g-force and pressure.     

Microplate methods for determination of serum cholesterol,high density lipoprotein cholesterol,triglyceride and apolipoproteins

Microtiter plate methods were developed for the enzymatic determination of serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG), and for the turbidometric determination of apolipoproteins. The micromethods resulted in accurate, precise values that were in good agreement with the conventional spectrophotometric assays. The coefficient of variation for TC determinations was 4.5% or less and bias was 5% or less. The lipid micromethod assays are sensitive to 10 mg/dL or less, and the apolipoprotein assay to 1 mg/dL. Less than 100 μL of serum suffices for TC, TG and apoprotein assays; HDL-C requires an additional 100 μL of serum. Advantages of the micromethods include reductions in assay time and in the amount of reagents required.     

Partial specific volume and preferential hydration of low density lipoprotein subfractions

We have determined the partial specific volume ( ) for five low density lipoprotein (LDL) subfractions (n=5–7) and evaluated preferential hydration (n=2) for LDL subfraction 3 in normolipoproteinemic subjects in order to characterize these highly atherogenic components of the human plasma lipoprotein spectra. Values for at 1 g were determined by sixth place density measurements of the solvent and lipoprotein solutions and carbon, hydrogen and nitrogen (CHN) absolute mass of the lipoprotein concentrations. Mean values for were 0.9757±0.0019, 0.9701±0.0007, 0.9674±0.0016, 0.9616±0.0016 and 0.9550±0.0025 ml/g for subfractions 1, 2, 3, 4 and 5, respectively. However, molecular densities (σ) obtained from ϱ(rho)=1/ for respective LDL subfractions were 1.0249, 1.0308, 1.0337, 1.0399 and 1.0471 g/ml, respectively. The preferential hydration of lipoprotein subfraction 3 (n=2) in NaCl/H₂O solutions was 2.9–4.8 wt percent, whereas values were much lower (0.3–0.6 wt percent) in NaCl/NaBr/H₂O solvent system. Unhydrated densities for LDL subfraction 3 (n=2) at 1 g (sixth-place density meter) were 1.0287 and 1.0269 g/ml, whereas at 200,000 × g (used in D₂O flotation ηF^o vs ϱ determinations) both values were 1.0308 g/ml, indicating that these similar LDL fractions have 23 and 53% higher compressibility than the solvent at 200,000 × g force. It was observed that the linearity of ηF^o vs ϱ may not be valid for solvents NaCl/NaBr/H₂O of density as high as 1.4744 g/ml. Thus, flotation velocity data using extreme salt concentrations (1.4744 g/ml and higher) may be viewed with caution.     

A new relationship between total/high density lipoprotein cholesterol and polyunsaturated fatty acids

Dietary and plasma fatty acids have been linked to total cholesterol but not to the ratio of total/high-density lipoprotein cholesterol (TC/HDLC). To evaluate the relationship between dietary and plasma levels of polyunsaturated fatty acids (PUFA) and TC/HDLC, we analyzed cross-sectional and longitudinal data using 519 plasma samples (50% men, 50% women) from subjects participating in the Framingham Heart Study and results from a study feeding diets rich in either n-6 linoleic acid or n-3 α-linolenic acid with or without fish oil supplements (n-3 derivatives). Values of TC/HDLC are inversely related to the percent of plasma PUFA when both variables are measured at the same time in different subjects,R=0.82,P<0.000001. PUFA in phospholipids increase in response to increased dietary intake of different PUFA, either n-3 or n-6 or fish oils. There was a highly significant inverse relationship between TC/HDLC and the percent of PUFA in phospholipids,R=0.97,P<0.001. The relationship was similar regardless of the source and type of dietary fatty acids. A similar relationship existed when only the baseline points were considered. When plasma PUFA % increases, either in response to a diet high in PUFA or across different subjects, TC/HDLC ratios decline. Evaluation of plasma fatty acid profiles and increased balanced dietary intake of PUFA to bring fatty acid profiles of subjects with low PUFA plasma levels closer to the profile of a healthy reference group is an effective approach to reduce high TC/HDLC. Reductions of more than 50% in TC/HDLC appear feasible with dietary modification alone. Further research into fatty acid metabolic activity may determine the biochemical basis of common dysplipidemias.     

Susceptibility of serum lipids to copper-induced peroxidation correlates with the level of high density lipoprotein cholesterol

As a first step in evaluating the significance of our recently developed method of monitoring the kinetics of copper-induced oxidation in unfractionated serum, we recorded the kinetics of lipid oxidation in the sera of 62 hyperlipidemic patients and analyzed the correlation between oxidation and lipid composition of the sera [high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides]. We used six factors to characterize the kinetics of oxidation, namely, the maximal absorbance of oxidation products (OD_max), the maximal rate of their production (V _max), and the time at which the rate was maximal (t _max) at two wave-lengths (245 nm, where 7-ketocholesterol and conjugated dienic hydroperoxides absorb intensely, and 268 nm, where the absorbance is mostly due to dienals). The major conclusions of our analyses are that: (i) Both OD_max and V _max correlate positively with the sum of concentrations of the major oxidizable lipids, cholesterol, and cholesteryl esters. (ii). The value of t _max, which is a measure of the lag preceding oxidation and therefore reflects the resistance of the serum lipids to copper-induced oxidation, exhibits a negative correlation with HDL cholesterol. Although this finding accords with the observation of shorter lags for HDL than for LDL, it is apparently inconsistent with the role of HDL as an antirisk factor in coronary heart diseases.     

High and low density lipoprotein cholesterol levels in hypercholesterolemic school children

To most fully explicate risk to coronary heart disease (CHD) in adults and children with elevated plasma total cholesterol, the levels of high and low density lipoprotein cholesterol (C-HDL, C-LDL) must be quantitated. This report focuses upon C-HDL and C-LDL levels in children identified in a lipid and lipoprotein sampling survey of 6,775 Princeton School children, by either total plasma cholesterol ≥205 mg/dl, the approximate 95th percentile for children 6–17 years of age, or age-, sex-, and race-specific 95th percentiles for cholesterol. Using the sex-, race-specific local 95th percentiles for C-HDL and C-LDL, the hypercholesterolemic children were separated into four categories according to whether they had elevations of both C-HDL and C-LDL, C-HDL only, C-LDL only, or neither. When selection for hypercholesterolemia was based on the overall 95th percentile (205 mg/dl), black children were more likely than white to have elevations of C-HDL only, which accounted for their hypercholesterolemia, p<.05, whereas white children were much more likely to have elevations of C-LDL only, than were black children, p<.005. However, when selection for hypercholesterolemia was based on age-, sex-, and race-specific 95th percentile cholesterol levels, there were no differences in the proportion of black and white children having elevations of C-HDL and C-LDL, accounting for their hypercholesterolemia. Elevated levels of C-HDL can explain apparent hypercholesterolemia in at least 16% of children, ages 6–17, who may putatively be at reduced, rather than increased CHD risk.     

Changing perceptions of hunger on a high nutrient density diet

Background  

People overeat because their hunger directs them to consume more calories than they require. The purpose of this study was to analyze the changes in experience and perception of hunger before and after participants shifted from their previous usual diet to a high nutrient density diet.     

Alterations of high density lipoprotein subclasses in obese subjects

The object of this study was to investigate the characteristics of lipid metabolism in obese subjects, with particular emphasis on the alteration of HDL subclass contents and distributions. A population of 581 Chinese individuals was divided into four groups (25 underweight subjects, 288 of desirable weight, 187 overweight, and 45 obese) according to body mass index (BMI). Apoprotein A-I (apoA-I) contents of plasma HDL subclasses were determined by 2-D gel electrophoresis associated with an immunodetection method. The concentrations of TG and the apoA-I content of pre-α₁-HDL were significantly higher (P<0.01 and P<0.01, respectively), but the levels of HDL cholesterol, and the apoA-I contents of HDL_2a and HDL_2b were significantly lower (P<0.01, P<0.05, and P<0.01, respectively) in obese subjects than in subjects having a desirable weight. Moreover, with the elevation of BMI, small-sized pre-α₁-HDL increased gradually and significantly, whereas large-sized HDL_2b decreased gradually and significantly. Meanwhile, the variations in HDL subclass distribution were more obvious with the elevation of TG levels in obese as well as overweight subjects. In addition, Pearson correlation analysis revealed that BMI and TG levels were positively correlated with pre-α₁-HDL but negatively correlated with HDL_2b. Multiple regression analysis also showed that TG concentrations were associated independently and positively with high pre-α₁-HDL and independently and negatively with low HDL_2b in obese and overweight subjects. The HDL particle size was smaller in obese and overweight subjects. The shift to smaller size was more obvious with the elevation of BMI and TG, especially TG levels. These observations, in turn, indicated that HDL maturation might be abnormal, and reverse cholesterol transport might be impaired. The first two authors contributed equally to this study.     

The evidence for the antiatherogenicity of high density lipoprotein in man

It has long been recognized that patients with clinical coronary heart disease (CHD) have, on average, higher concentrations of plasma very low density and low density lipoproteins than do healthy subjects. The same, studies clearly demonstrated that coronary victims tend also to have low plasma concentrations of high density lipoprotein (HDL). It is only recently, however, that the possible significance of this second observation has been examined. Direct evidence for an inverse relationship between HDL cholesterol concentration and the prevalence of clinical CHD, independent of other plasma lipoproteins, has been provided by the Honolulu Heart and Cooperative Lipoprotein Phenotyping Studies. The Tromsø Heart and Framingham Studies subsequently demonstrated that this relationship precedes the clinical manifestation of coronary disease. More recently, angiographic studies have confirmed that the severity of existing coronary atherosclerosis is inversely related to HDL cholesterol concentration. Other investigations have shown that coronary victims also have low mean concentrations of apolipoproteins AI and AII (the major protein components of HDL), although the reduction of apoAI concentration may be less marked than that of HDL cholesterol, and preliminary findings from Tromsø have suggested that apolipoprotein AI may be less powerful than HDL cholesterol as a predictor of CHD. Such observations have supported the proposal that HDL may exert a protective effect against coronary atherosclerosis. Final confirmation (or otherwise) of this hypothesis, however, must await the results of carefully controlled animal experiments and of regression studies in patients with angiographically defined atherosclerosis.     

Vitamin E reduces cholesterol esterification and uptake of acetylated low density lipoprotein in macrophages

The effects of vitamin E on cholesteryl ester (CE) metabolism in 1774 cells were examined. Pretreatment of 1774 cells with vitamin E at concentrations above 50 μM significantly decreased acetylated low density lipoprotein (LDL)-induced incorporation of [¹⁴C]oleate into CF in cells in a dose-dependent manner. This was partly due to vitamin E Also significantly inhibiting the uptake of [³H]CE-labeled acetylated LDL by 1774 cells. A trend existed toward suppression of acyl-CoA:cholesterol acyltransferase (ACAT) activity in the cell lysate at high vitamin E concentration, but there was no effect on hydrolysis of CE. These data indicate that vitamin E reduces the uptake of modified LDL and suppresses ACAT activity, resulting in less cholesterol esterification in macrophages; a novel mechanism underlying the antiatherogenic properties of vitamin E.     

Nonalcoholic components in wine reduce low density lipoprotein cholesterol in normocholesterolemic rats

Using an experimental model that enables the effects of alcohol to be distinguished from the effects of the nonalcoholic components present in wine, we determined whether wine has effects other than those of alcohol on the metabolism of cholesterol. Male rats were fed a standard diet and had free access to water and either wine or an equivalent alcohol solution for 45 d or 6 mon. Alcohol intake was similar in the two groups of animals. Consumption of the alcohol solution or wine did not influence plasma cholesterol or high density lipoprotein-cholesterol. At 45 d, the consumption both of wine and of alcohol solution reduced low density lipoprotein (LDL)-cholesterol and very low density lipoprotein cholesterol. At 6 mon, only the rats that consumed wine had reduced LDL-cholesterol. After 45 d of consuming alcohol solution, total cholesterol in the aorta was significantly increased mainly as a result of the rise in free cholesterol. In the aorta, the effect of wine consumption was similar to the effect of alcohol solution consumption, although it was less intense. The only clear effect that could be ascribed to the nonalcoholic components in wine was that the LDL-cholesterol was reduced in the long term, although aortic cholesterol was not.     

Effects of estrogens and progestins on high density lipoproteins

High density lipoprotein (HDL) levels are known to be higher in women than in men, and to increase with estrogen use. To assess the effects of estrogens on HDL subspecies, analytic ultracentrifuge measurements of HDL were compared in 11 menopausal estrogen users and 16 controls. The difference in mean schlieren patterns between the groups showed a significantly higher level of HDL with flotation rate (F _1.20 ^o )>1.5 (predominantly HDL₂) in the users. This was similar to the difference in HDL seen between nonusers of hormones and age-matched males. A previous study had shown that users of combination oral contraceptives had increased levels of HDL with F _1.20 ^o ≤3.5 (primarily HDL₃) suggesting that the estrogen effect on HDL is altered by the presence of added progestin. The progrestin effect was studied here in more detail in two women with type V hyperlipoproteinemia treated with norethindrone acetate. Reduction in serum triglyceride was accompanied by a reduction in HDL, predominantly in the less dense species (HDL₂). Among groups of oral contraceptive and noncontraceptive estrogen and progestin users whose HDL-cholesterol levels have been reported recently, there was a direct correlation (r=0.86, p<.001) between mean HDL-cholesterol and triglyceride levels. Endogenous hormonal influences on HDL were assessed by serum hormone and lipoprotein measurements at weekly intervals during two consecutive menstrual cycles in four healthy females. An increase in HDL of highest flotation rate (F _1.20 ^o 5–9) was seen, which corresponded with the time of ovulation raising the possibility of pituitary as well as gonadal hormone effects on HDL.     

Effect of liposome-encapsulated hemoglobin on triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein cholesterol measurements

The present study investigated the effect of liposome-encapsulated hemoglobin (LEH), an experimental oxygen-carrying resuscitation fluid, on triglyceride, total cholesterol, and low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol measurements. In vivo, the intravenous infusion of LEH (5.6 mL/kg, n=6) elevated serum triglycerides (+92% vs. baseline, P<.05), total cholesterol (+25% vs. baseline, P<.01), LDL cholesterol (+72% vs. baseline, P<.01) and had no effect on serum HDL cholesterol. In addition, LEH did not alter the elevation in serum triglycerides (+302% vs. baseline, P<.01) and LDL cholesterol (+86% vs. baseline, P<.01) induced by lipopolysaccharide (3.6 mg/kg, i.v., n=6). Ex vivo, measurements of triglycerides and total cholesterol as well as LDL and HDL cholesterol in whole blood from naive rats were not changed by the addition of LEH (0–50%, n=6). In vitro, the addition of a fixed concentration of LEH (50%, n=6) to varying concentrations of cholesterol solution (0–50%), or vice versa, had no effect on cholesterol determination. It is therefore concluded that LEH only minimally affects serum levels of triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol and does not interfere with their measurement.     

The role of high density lipoprotein apolipoprotein CII in triglyceride metabolism

The purpose of these studies was (a) to examine the relationship between total plasma triglycerides (TG) and the amount of apolipoprotein CII (apo CII) in triglyceride rich lipoproteins (TRL), and (b) to determine whether TRL could be enriched with apo CII in vitro. In 13 patients with primary endogenous hypertriglyceridemia, (log₁₀) total plasma TG correlated inversely with the amount of apo CII per unit very low density lipoprotein (VLDL) protein (r=−0.76;p<0.005) and VLDL TG (r=−0.75; p<0.005). The potency of VLDL to activate milk lipoprotein lipase (LPL) in hydrolyzing triolein was studied in vitro. LPL activator potency per unit VLDL protein or VLDL TG correlated inversely with (log₁₀) total plasma TG (r=−0.86 and r=−0.76, respectively; p<0.005). LPL activator potency per nM VLDL apo CII also correlated inversely with (log₁₀) total plasma TG (r=−0.49; p<0.01). In seven patients with familial type V hyperlipoproteinemia, the average amount of apo CII in TRL protein was subnormal (5.86±0.62% vs 10.0±0.51% in normal subjects). The higher the (log₁₀) total plasma TG, the lower was the apo CII content in TRL protein (r=−0.93; p<0.01). To determine the factors governing the distribution of apo CII between lipoproteins and whether TRL could be enriched with apo CII, five approaches were undertaken: (a)¹²⁵I apo CII was added to mixtures of VLDL and HDL. The amount of labelled apo CII in VLDL was proportional to the ratio of VLDL to HDL. (b) TRL from four patients with familial type V hyperlipoproteinemia was incubated with high density lipoprotein (HDL) from a normal subject. An increase in the TRL/HDL ratio was associated with transfer of apo CII from HDL to TRL and a reciprocal transfer of non-apo CII protein from TRL to HDL. Net apo CII enrichment of TRL protein was possible below a HDL/TRL protein ratio of ca. 6 under the experimental conditions. (c) A fixed amount of normal plasma feed of TRL was incubated with different amounts of TRL from two patients with familial type V hyperlipoproteinemia. The amount of apo CII that transferred from normal TRL free plasma to the patient’s TRL was proportional to the amount of TRL in the mixture. (d) A doubling and tripling in the amount of apo CII in TRL was found when apo CII was added directly to TRL from a normal subject and TRL from a patient with familial type V hyperlipoproteinemia, respectively. (e) When apo CII was added directly to normal plasma and plasma from a patient with primary type IV hyperlipoproteinemia, the peptide was taken up mainly by VLDL and HDL, indicating enrichment of these fractions. The distribution of the added apo CII in each lipoprotein fraction resembled the distribution in the native plasma. TRL was isolated after addition of apo CII to plasma from two patients with familial types IV and V, respectively. Enrichment of TRL with apo CII was associated with an approximate 1.5-fold increase in the LPL activator potency per unit TRL protein. These studies suggest that firstly, the amount of apo CII in TRL is inversely related to the severity of hypertriglyceridemia. Secondly, the distribution of apo CII between TRL and HDL is governed by the mass ratios of these two lipoprotein classes. Thirdly, plasma TRL and HDL have a reserve binding capacity of apo CII and fourthly, it is possible to enrich these lipoproteins with this functionally important peptide. Whether net enrichment of TRL with apo CII and also an increase in its biological activity to activate LPL in vitro is related to increased in vivo catabolic rate requires to be determined.     

Effect of dietary palm oil and its fractions on rat plasma and high density lipoprotein lipids

Male Sprague Dawley rats were fed semipurified diets containing 20% fat for 15 weeks. The dietary fats were corn oil, soybean oil, palm oil, palm olein and palm stearin. No differences in the body and organ weights of rats fed the various diets were evident. Plasma cholesterol levels of rats fed soybean oil were significantly lower than those of rats fed corn oil, palm oil, palm olein or palm stearin. Significant differences between the plasma cholesterol content of rats fed corn oil and rats fed the three palm oils were not evident. HDL cholesterol was raised in rats fed the three palm oil diets compared to the rats fed either corn oil or soybean oil. The cholesterol-phospholipid molar ratio of rat platelets was not influenced by the dietary fat type. The formation of 6-keto-PGF_1α was significantly enhanced in palm oil-fed rats compared to all other dietary treatments. Fatty acid compositional changes in the plasma cholesterol esters and plasma triglycerides were diet regulated with significant differences between rats fed the polyunsaturated corn and soybean oil compared to the three palm oils.     

Very low density lipoprotein secretion by cultured hepatocytes of rabbits fed purified or autoxidized cholesterol

The main objectives of this study were to compare the effects of dietary commercial cholesterol (containing 5% of oxidized cholesterol derivatives) and purified cholesterol on the secretion rate of very low density lipoprotein apolipoproteins and lipids by cultured rabbit hepatocytes and to verify the hypothesis that products of cholesterol autoxidation stimulate the rapid development of hypercholesterolemia. Rabbits fed dietary (old) commercial cholesterol for six weeks showed a fivefold increase in the serum concentration of cholesterol compared with that in purified cholesterol-fed rabbits. The secretion rates of very low density lipoprotein total protein and very low density lipoprotein [³H]apolipoproteins were similar for the hepatocytes of these two cholesterol-fed groups of animals and were two- and threefold greater, respectively, than for cells from control rabbits. Cholesteryl ester content of the hepatocytes from dietary (old) commercial cholesterol-fed rabbits was dramatically increased in comparison with hepatocytes from control and purified cholesterol-fed rabbits. The elevated intracellular cholesteryl ester content is assumed to account for such an increase of very low density lipoprotein-cholesteryl ester secretion by cells prepared from dietary (old) commercial cholesterol-fed rabbits. These effects appear to be caused by activation of cholesterol esterification by oxidized cholesterol derivatives. The rapid development of hypercholesterolemia induced by dietary (old) commercial cholesterol is associated, at least in part, with the stimulated production of hepatic very low density lipoprotein apolipoproteins and cholesteryl esters.