Quantitation of baboon lipoproteins by high performance gel exclusion chromatography

High performance liquid chromatography with gel exclusion columns was used for quantitative measurement of plasma lipoproteins. A combination of columns TKS 4000 PW and 3000 PW gave good separation of very low (VLDL), low (LDL) and high (HDL) density lipoproteins. The area under each lipoprotein peak detected by absorbance at 280 nm was measured by digitizing and was expressed as cm². Purified lipoprotein standards isolated by ultracentrifugation were also chromatographed in increasing concentrations. The area under the lipoprotein standard peak was linearly related to the amount of total protein over a wide range. The areas of most of the measured plasma lipoproteins were within the linear range. The relationship between the area and the amount of protein for each standard was used to quantitate the amount of protein and was expressed as mg/dl plasma. This technique is simple and requires a small amount of plasma. The validated technique was applied to a large population of pedigreed baboons. An average plasma lipoprotein profile of feral baboons on the chow diet was characterized by a high level of HDL (90.9±30.7 mg/dl) with a lesser amount of LDL (29.1±13.2 mg/dl). VLDL was present in much lower concentration (8.6±2.6 mg/dl). Feeding a high cholesterol and high saturated fat (HCHF) diet raised both LDL (1.5-fold) and HDL levels (1.3-fold) without changing VLDL levels. Progeny of sires with low response to dietary cholesterol increased their HDL protein when challenged with HCHF diet without any change in their LDL or VLDL. Progeny of high-responding sires, however, had increases in both their HDL and LDL levels when challenged with HCHF diet. The survey of lipoprotein profiles of the pedigreed baboon colony disclosed a number of animals with interesting and unusual lipoprotein patterns.     

Increased amounts of cholesterol precursors in lipoproteins after ileal exclusion

Serum cholesterol precursor sterols reflect the activity of cholesterol synthesis. In this study, squalene, methyl sterol and lathosterol contents were studied in very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) of heterozygous familial hypercholesterolemia patients without and with ileal bypass. The contents of lathosterol and all methyl sterols (lanosterol, Δ^8,24-dimethylsterol, Δ⁸-dimetylsterol, Δ⁸-methostenol and methostenol), but not of squalene were increased in all lipoproteins by ileal bypass. The increase in the free methyl sterols was more marked than that in the esterified ones. The percentage esterification of the methyl sterols was highest in HDL and lowest in VLDL. Lipoprotein methyl sterol contents were positively correlated with each other and with cholesterol synthesis. The methyl sterols were slightly concentrated in LDL, and squalene strongly concentrated in VLDL. It is concluded that long-term stimulation of cholesterol synthesis increases the methyl sterols in all lipoproteins.     

The effect of dietary lipid on the lipoprotein status of the mongolian gerbil

The Mongolian gerbil,Meriones unguiculatus, may be a suitable animal model for the investigation of dietary lipid effects on cholesterol metabolism. The effects of dietary cholesterol, and its possible interaction with the type of dietary fat, on the lipoprotein status of this animal have not been examined previously. In the present research, the effects of adding 0.5% cholesterol to diets high in saturated (19.5% beef tallow: 0.5% safflower oil) or polyunsaturated (20% safflower oil) fats on the lipoprotein status of the gerbil were determined after 11 and 22 days of feeding. Lipoproteins (VLDL, LDL and HDL) were separated by sequential ultracentrifugation. Their cholesterol, phospholipid and protein concentrations were determined colorimetrically. In the absence of 0.5% cholesterol, safflower oil lowered the concentration (mg/100 ml) of cholesterol in each of the VLDL, LDL and HDL relative to beef tallow (BT) without greatly influencing the cholesterol distribution amongst them. The HDL carried the majority of the serum cholesterol and the VLDL transported the smallest amount. However, inclusion of 0.5% dietary cholesterol resulted in a redistribution of cholesterol amongst the lipoproteins so that the VLDL and LDL became the major and the HDL the minor carriers. Dietary cholesterol also brought about a rise in the VLDL and LDL concentrations (mg/100 ml) of cholesterol, phospholipid and protein and altered the VLDL and LDL compositions. No such changes were observed in the HDL, indicating that the HDL are relatively resistant to any of the possible effects of cholesterol feeding measured in this experiment. The specific mechanisms responsible for the changes observed in the lipoprotein status of the gerbil remain to be elucidated. Presented in part at the Triennial Joint Meeting of the AIN/ASCN/CSNS, July 1982     

Hypolipidemic activity of 6-alkoxycarbonyl-3-aryl-1,3,5-triazabicyclo[3.1.0]hexane-2,4-diones and 2-alkoxycarbonyl-5-aryl-1,3,5-triazine-4,6(1H,5H)-diones in rodents

Significant hypolipidemic activity was demonstrated by 6-ethoxycarbonyl-3-phenyl-1,3,5-triazabicyclo[3.1.0]hexane-2,4-dione, 2-ethoxycarbonyl-5-phenyl-1,3,5-triazine-4,6(1H,5H)-dione and 2-ethoxycarbonyl-5-(4-chlorophenyl)-1,3,5-trizine-4,6(1H,5H)-dione in rodents at 20 mg/kg/day. These agents lowered serum cholesterol and triglyceride levels by approximately 40% in mice after 16 d. Tissue lipids in rat liver, small intestinal mucosa, aortic wall and feces were reduced by treatment with the agents. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol levels were reduced in the rat; high density lipoprotein (HDL) cholesterol levels were elevated after 14 d of treatment. The activities of regulatory enzymes,e.g., acetyl-CoA synthetase, acyl-CoA:cholesterol acyltransferase, cholesterol 7α-hydroxylase,sn-glycerol-3-phosphate acyltransferase, phosphatidylate phosphohydrolase and heparin-induced lipoprotein lipase, involved inde novo synthesis of hepatic lipids were affected by the agents. The new compounds may represent another class of potentially useful hypolipidemic agents for the treatment of atherosclerosis since HDL cholesterol levels were increased and VLDL and LDL cholesterol levels were lowered by some of the agents.     

Aerobic Exercise Improves Reverse Cholesterol Transport in Cholesteryl Ester Transfer Protein Transgenic Mice

We analyzed the effect of a 6-week aerobic exercise training program on the in vivo macrophage reverse cholesterol transport (RCT) in human cholesteryl ester transfer protein (CETP) transgenic (CETP-tg) mice. Male CETP-tg mice were randomly assigned to a sedentary group or a carefully supervised exercise training group (treadmill 15 m/min, 30 min sessions, five sessions per week). The levels of plasma lipids were determined by enzymatic methods, and the lipoprotein profile was determined by fast protein liquid chromatography (FPLC). CETP activity was determined by measuring the transfer rate of ¹⁴C-cholesterol from HDL to apo-B containing lipoproteins, using plasma from CETP-tg mice as a source of CETP. The reverse cholesterol transport was determined in vivo by measuring the [³H]-cholesterol recovery in plasma and feces (24 and 48 h) and in the liver (48 h) following a peritoneal injection of [³H]-cholesterol labeled J774-macrophages into both sedentary and exercise trained mice. The protein levels of liver receptors were determined by immunoblot, and the mRNA levels for liver enzymes were measured using RT-PCR. Exercise training did not significantly affect the levels of plasma lipids or CETP activity. The HDL fraction assessed by FPLC was higher in exercise-trained compared to sedentary mice. In comparison to the sedentary group, a greater recovery of [³H]-cholesterol from the injected macrophages was found in the plasma, liver and feces of exercise-trained animals. The latter occurred even with a reduction in the liver CYP7A1 mRNA level in exercised trained animals. Exercise training increased the liver LDL receptor and ABCA-1 protein levels, although the SR-BI protein content was unchanged. The RCT benefit in CETP-tg mice elicited by exercise training helps to elucidate the role of exercise in the prevention of atherosclerosis in humans.     

Increases in hyperlipoproteinemia,disturbances in cholesterol metabolism and atherosclerosis induced by dietary restriction in rabbits fed a cholesterol-rich diet

The influence of dietary restriction on cholesterol transport and metabolism was investigated in rabbits given standard or cholesterol-rich diets (0.2 g cholesterol/kg body weight daily) eitherad libitum or with 50% caloric ration. Dietary restriction which has only a slight influence in control rabbits markedly aggravated the disturbances induced by exogenous cholesterol. With limited feeding, control rabbits presented a moderate increase in plasma cholesterol, whereas marked aggravation of hypercholesterolemia was observed in cholesterol-fed rabbits. Analysis of the lipoprotein profile showed that the excess of plasma cholesterol with the restricted cholesterol-rich diet corresponded to an increase in the concentration of very low density lipoprotein (VLDL) and low density lipoproteins (LDL) without any additional changes in the composition of these lipoproteins. No significant change appeared in the high density lipoprotein (HDL) concentration. The parameters of cholesterol metabolism were determined, from the curves of [³H] cholesterol radioactivity decrease, using a two-pool model. The increase in cholesterol turnover rate induced by the cholesterol-rich diet was accentuated by dietary restriction, whereas rabbits on standard restricted diet showed a slight decrease. The large increase in the size of both pools A and B in cholesterol-fed rabbits was even more pronounced with limited feeding. Dietary restriction induced additional accumulation of cholesterol in the aortic wall and the grade of the lesions was also aggravated.     

Chronic Exercise Reduces CETP and Mesterolone Treatment Counteracts Exercise Benefits on Plasma Lipoproteins Profile: Studies in Transgenic Mice

Regular exercise and anabolic androgenic steroids have opposing effects on the plasma lipoprotein profile and risk of cardio-metabolic diseases in humans. Studies in humans and animal models show conflicting results. Here, we used a mice model genetically modified to mimic human lipoprotein profile and metabolism. They under-express the endogenous LDL receptor gene (R1) and express a human transgene encoding the cholesteryl ester transfer protein (CETP), normally absent in mice. The present study was designed to evaluate the independent and interactive effects of testosterone supplementation, exercise training and CETP expression on the plasma lipoprotein profile and CETP activity. CETP/R1 and R1 mice were submitted to a 6-week swimming training and mesterolone (MEST) supplementation in the last 3 weeks. MEST treatment increased markedly LDL levels (40%) in sedentary CETP/R1 mice and reduced HDL levels in exercised R1 mice (18%). A multifactorial ANOVA revealed the independent effects of each factor, as follows. CETP expression reduced HDL (21%) and increased non-HDL (15%) fractions. MEST treatment increased the VLDL concentrations (42%) regardless of other interventions. Exercise training reduced triacylglycerol (25%) and free fatty acids (20%), increased both LDL and HDL (25–33%), and reduced CETP (19%) plasma levels. Significant factor interactions showed that the increase in HDL induced by exercise is explained by reducing CETP activity and that MEST blunted the exercise-induced elevation of HDL-cholesterol. These results reinforce the positive metabolic effects of exercise, resolved a controversy about CETP response to exercise and evidenced MEST potency to counteract specific exercise benefits.     

Hypolipidemic activity of the surfactants aminimides,and their effects on lipid metabolism of rodents

A series of short chain fatty acid derivatives of aminimides were shown to possess hypolipidemic activity in rats and mice. Most of the agents tested lowered both serum cholesterol and triglyceride levels by at least 30% in mice and were effective in hyperlipidemic induced mice. 1,1-Dimethyl-1-(2-hydroxypropyl)-amine mersitimide lowered serum cholesterol levels 41% and serum triglyceride levels 56% at 20 mg/kg/day I.P. after 16 days. The same agent was active orally when administered to rats with a 38% reduction in serum cholesterol and a 52% reduction in serum triglycerides after 14 days. The agents inhibited liver acetyl CoA synthetase, ATP dependent citrate lyase and phosphatidate phosphohydrolase activities in vitro and in vivo. Reduction of cholesterol, triglycerides, neutral lipids and phospholipid levels were noted in the livers of mice treated for 16 days. In rat studies, cholesterol, triglyceride and phospholipid levels were reduced in liver, small intestine and the feces after two weeks' dosing. The cholesterol content was reduced in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions but elevated in the high density lipoproteins (HDL). Triglyceride levels were lowered in the VLDL, and neutral lipid levels were reduced in the chylomicron and VLDL fractions.     

The distribution of dietary plant sterols in serum lipoproteins and liver subcellular fractions of rats

Rats were fed plant sterols containing campesterol and β-sitosterol in the different proportions, and their distribution in serum lipoproteins and in liver subcellular fractions was determined. In serum lipoproteins, the percentage as well as the concentration of plant sterols increased with the increase in the density of lipoproteins. Thus, high density lipoprotein (HDL) contained the highest and very low density lipoprotein (VLDL), the lowest. Also, there were distinct differences in the ratio of campesterol to sitosterol among lipoproteins, it was the highest in VLDL and lowest in HDL. Quantitatively, more than 75% of campesterol and 80% of sitosterol were carried in HDL; the values were significantly different from those of cholesterol (ca. 70%) in relation to total cholesterol. The distribution of plant sterols in liver subcellular fractions was virtually the same with that of cholesterol. Both nuclei and microsomes contained approximately 40% of total plant stetols. A preliminary part of the study was presented at the First Congress of the Federation of Asian and Oceanian Biochemists in Nagoya, October 1977.     

Studies on the transfer of tocopherol between lipoproteins

The net transfer of labeled α-tocopherol from donor to acceptor lipoproteins at physiological concentrations was investigated. Labeled lipoproteins were isolated i) followingin vitro addition of [3,4-³H]all rac-α-tocopherol to plasma, or ii) from plasma obtained 12–16 h after ingestion by normal subjects of an oral dose (100 mg each) of 2R,4′R,8′R-α-[5,7-(C²H₃)₂]tocopheryl acetate and 2S,4′R′,R-α-[5-C²H₃]tocopheryl acetate. A constant amount (on a protein basis) of labeled lipoprotein was incubated with an increasing amount of unlabeled acceptor lipoprotein for 2 h at 37°C. No discrimination between stereoisomers of α-tocopherol was detected. Labeled VLDL and labeled LDL (very low and low density lipoproteins, respectively) tended to retain their labeled tocopherol. Labeled high density lipoproteins (HDL) readily transferred the labeled tocopherol to VLDL (>60% transferred), while the transfer to LDL was dependent upon the ratio of labeled HDL/LDL with a lower net transfer at higher ratios. This dependency of the distribution of tocopherol upon the ratio of HDL/LDL was also observedin vivo. The tocopherol/mg HDL protein was measured in 11 subjects with varying HDL levels. As the %HDL in the plasma increased from 14 to 50%, the tocopherol/HDL protein also increased (r²=0.37,P<0.05).     

Lipid metabolism and tissue composition in Atlantic salmon (Salmo salar L.)—Effects of capelin oil, palm oil, and oleic acid-enriched sunflower oil as dietary lipid sources

Triplicate groups of Atlantic salmon (Salmo salar L.) were fed four diets containing different oils as the sole lipid source, i.e., capelin oil, oleic acid-enriched sunflower oil, a 1∶1 (w/w) mixture of capelin oil and oleic acid-enriched sunflower oil, and palm oil (PO). The β-oxidation capacity, protein utilization, digestibility of dietary fatty acids and fatty acid composition of lipoproteins, plasma, liver, belly flap, red and white muscle were measured. Further, the lipid class and protein levels in the lipoproteins were analyzed. The different dietary fatty acid compositions did not significantly affect protein utilization or β-oxidation capacity in red muscle. The levels of total cholesterol, triacylglycerols, and protein in very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL), and plasma were not significantly affected by the dietary fatty acids. VLDL, LDL, and HDL fatty acid compositions were decreasingly affected by dietary fatty acid composition. Dietary fatty acid composition significantly affected both the relative fatty acid composition and the amount of fatty acids (mg fatty acid per g tissue, wet weight) in belly flap, liver, red and white muscle. Apparent digestibility of the fatty acids measured by adding yttrium oxide as inert marker, was significantly lower in fish fed the PO diet compared to the other three diets.     

Diurnal variation of plasma methyl sterols and cholesterol in the rat: Relation to hepatic cholesterol synthesis

Free cholesterol of plasma low density lipoproteins (LDL) and high density lipoproteins (HDL) of the rat was high and that of plasma very low density lipoproteins (VLDL) was low during the dark period of the diurnal cycle. Variations in the esterified plasma sterols were inconsistent. Free methyl sterols were high in all lipoproteins during the dark phase. Simultaneously, the incorporation of¹⁴C-acetate into nonsaponifiable sterols and the concentrations of free methyl sterols and cholesterol in the liver were elevated.     

Lipoprotein lipid and protein synthesis in experimental nephrosis and plasmapheresis. I: Studies in rat in vivo

The incorporation of L-4,5-[³H]leucine into the ultracentrifugally separated apolipoproteins of very low, low, and high density lipoproteins (VLDL, LDL, HDL) and into serum albumin was found three-to four-fold higher in nephrotic than in normal rats one hour after intravenous injection. Incorporation of leucine into the circulating lipids was negligible. Increases of similar magnitude were obtained in the incorporation of simultaneously injected 1,5[¹⁴C] citrate into the lipids of VLDL, LDL, and HDL of nephrotic rats. Of the citrate carbons incorporated into serum and liver lipids, the proportion in cholesterol was higher in nephrotic rats when compared to normal rats. The incorporation of both precursors into total proteins and lipids of the liver vs. the incorporation into the lipoproteins was relatively lower in nephrotic than in control rats, indicating a preferential channeling into secretable products. The occurrence of enhanced new lipid synthesis in nephrosis was corroborated by the finding of markedly enhanced synthesis of lipoprotein-borne fatty acids and cholesterol from³H₂O. These results point out that while leucine is not an efficient in vivo precursor of lipoprotein lipids in nephrosis, de novo lipogenesis proceeds from other precursors. Similar trend of changes, though of smaller magnitude, was elicited in rats after double plasmapheresis, 18 hr apart, when measured 3 hr after the second plasma withdrawal. This indicates that the loss of circulating proteins either by direct removal or through kidney lesion stimulates the compensatory hepatic response involving excessive lipoprotein synthesis. Time-course studies showed that peak incorporation of leucine and citrate into the protein and lipid components of lipoproteins, respectively, as well as into serum albumin, occurred coincidentally 3 hr after the second plasmapheresis, suggesting an interdependence of the enhanced protein and lipid synthesis.     

Effect of KCD-232, a new hypolipidemic agent,on serum lipoprotein changes in hepatoma-bearing rats

Changes in serum lipoprotein profiles were characterized in Donryu rats subcutaneously implanted with an ascites hepatoma line of AH109A cells and the effect of a new hypolipidemic agent with a structure of 4-(4′-chlorobenzyloxy)benzyl nicotinate (KCD-232) was estimated. With the growth of hepatoma for periods of up to three weeks, a striking decrease in the high density lipoprotein (HDL) fraction and an enormous increase in the VLDL+LDL (very low density lipoprotein+low density lipoprotein) fraction were found in hepatoma-bearing rats when either precipitation method or electrophoresis was used. These lipoprotein profiles were not influenced by sex. Judging from the electrophoretogram, the increase in VLDL+LDL fraction was due mainly to an increase in LDL fraction. The oral administration of KCD-232 significantly suppressed the hepatoma-induced increase in VLDL+LDL with little or no influence on the hepatoma-induced decrease in HDL. There existed a positive correlation between the hepatoma weight and (VLDL+LDL)-cholesterol concentration and a negative one between hepatoma and HDL-cholesterol.     

Composition and concentration of lipoproteins in the serum of normal rats and rats deficient in essential fatty acids

A comparison is made of the concentration and chemical composition of serum lipoproteins of normal rats and rats deficient in essential fatty acids. The concentration of very low density lipoproteins (VLDL) and of low density lipoproteins (LDL) in serum of deficient rats is about half that found in normal rats, but the concentration of high density lipoproteins (HDL) is higher than normal and they contain an increased amount of cholesterol esters. The proportion of cholesterol that is esterified is much greater than normal in the serum of deficient rats. The deficiency of essential fatty acids also appears to result in compensating changes occurring in the composition of serum lipoproteins. In both VLDL and LDL of deficient rats the proportion of protein is raised and that of phospholipid lowered compared to normal, while the proportions of trigly ceride and cholesterol esters are unchanged.     

Regulation of lung surfactant cholesterol metabolism by serum lipoproteins

The isolated perfused rat lung was used as an experimental model in the study of the lipoprotein regulation of surfactant cholesterol metabolism. Addition of low density lipoproteins (LDL) to the perfusion medium at a cholesterol concentration of 0.5 mM had no inhibitory effect on [1-¹⁴C]-acetate incorporation into cholesterol of either the surfactant or residual fractions. Increasing the concentration of cholesterol in the medium to 2.5 mM resulted in significant inhibition of incorporation into cholesterol of both fractions. A similar inhibition resulted when lungs were perfused with 2.5 mM cholesterol in the form of high density lipoproteins (HDL). No inhibition of fatty acid synthesis, measured as incorporation into cholesteryl esters, was observed. The rate of uptake by perfused lung of cholesterol from both high and low density lipoproteins was similar. Competitive binding studies with¹²⁵I-labeled lipoproteins indicated the existence of lung receptors for both classes of lipoprotein. The rate of uptake of the apoprotein moiety of low density lipoproteins was significantly greater than that of high density lipoproteins. These data suggest that lung cholesterol metabolism may be subject to regulation by both low and high density serum lipoproteins.     

Net lipid transfer between lipoproteins in fish-eye disease plasma supplemented with normal high density lipoproteins

Native fish-eye disease plasma, which is deficient of both high density lipoproteins (HDL) and lecithin-cholesterol acyltransferase activity (α-LCAT), processing the free cholesterol of these lipoproteins, has been supplemented with normal isolated HDL₂ or HDL₃ and incubated in vitro at 37 C. After incubation for 0,7.5 and 24 hr the very low density (VLDL) and low density (LDL) lipoproteins as well as HDL were isolated, and their contents of triglycerides, phospholipids and free, esterified and total cholesterol were quantified. The resulting net mass transfer of the different lipids revealed a functioning transfer of cholesteryl esters and all other analyzed lipids between the lipoproteins, although no de novo esterification of the HDL cholesterol by LCAT in this plasma occurred. In accordance with previous findings there was a functioning esterification process of the free cholesterol of the combined VLDL and LDL of fish-eye disease plasma. The present results make it reasonable to conclude that the lack of HDL cholesterol esterification in this disease is not a result of a deficiency of cholesteryl ester transfer or lipid transfer activities.     

Isolation of human serum low-density lipoproteins with the aid of an immune-specific adsorber

Human serum lipoproteins containing B-protein have been isolated using an immunoadsorber. Bromoacetyl cellulose was combined with pure antibodies to low density lipoprotein (LDL) and an immunoadsorber of high capacity was obtained. With 1 g of this immunoadsorber all LDL and very low density lipoprotein (VLDL) from 30 ml pooled human serum were adsorbed and then eluted with glycine-HCl buffer pH 3.2 at 0 C. The isolated lipoproteins were investigated by electrophoresis, immunodiffusion and ultracentrifugation, and found to be identical to LDL+VLDL isolated by ultracentrifugation.     

Glycosphingolipids of human plasma lipoproteins

The content and structure of glycosphingolipids (GSL) in human plasma lipoproteins were studies. The quantitative distribution of the neutral GSL(Glc-Cer, Gal-Glc-Cer, Gal-Gal-Glc-Cer, and GalNAc-Gal-Gal-Glc-Cer) and the principal ganglioside (AcNeu-Gal-Glc-Cer) within the different lipoprotein classes was similar to that of whole plasma. The total amounts (μmol glucose/100 ml plasma) of GSL in the plasma lipoproteins of three normal subjects were VLDL (very low density lipoproteins) (trace to 0.46), LDL (low density lipoproteins) (1.08–1.48), HDL₂ (high density lipoproteins₂) (0.62–0.85), and HDL₃ (high density lipoproteins₃) (trace to 0.28). In subjects with Lp(a) lipoproteins, HDL₂ rather than HDL₃ contained most of the GSL in HDL. When the data were corrected for differences in the plasma concentrations of the lipoproteins, the total amounts of GSL(nmol glucose/mg lipoprotein cholesterol) were VLDL(trace to 21.20), LDL(11.70–15.36), HDL₂(8.50–9.10), and HDL₃(3.12). No GSL were detected in lipoprotein deficient plasma. Mass spectrometry of the trimethylsilyl derivatives of the GSL in LDL showed major fragment ions characteristic of their individual structural components. The elevated plasma levels of the GSL(2–18 fold), in a homozygote for familial hypercholesterolemia, resided in LDL which contained an absolute increase (per mg lipoprotein cholesterol) of GSL. Most, if not all, of the plasma GSL are associated with plasma lipoproteins and may have an important role in their biological functions.     

Changes in high density lipoprotein subfraction lipids during neutral lipid transfer in healthy subjects and in patients with insulin-dependent diabetes mellitus

While it is known that the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to the apo B-containing lipoproteins is increased in patients with diabetes, the extent to which the various lipoprotein fractions engage in neutral lipid exchange and the magnitude to which triglyceride (TG) is translocated is not known. To examine in greater detail neutral lipid net mass transfer in diabetes, the HDL subfractions and the apo B-containing lipoproteins were separated, and the net mass transfer of CE and TG was compared to that of control subjects. In both groups, bidirectional transfer of CE from HDL₃ to very low density lipoprotein (VLDL) + low density lipoprotein (LDL) and of TG from VLDL+LDL to HDL₃, took place, but this process was significantly greater (P<.01) in insulin-dependent diabetes mellitus (IDDM). In contrast, CE and TG accumulated in HDL₂ to a similar degree in normal and IDDM subjects. In recombination experiments with each of the apo B-containing lipoproteins, IDDM VLDL had a greater capacity to facilitate the exchange of core lipids from both IDDM and control HDL₃: on the other hand, LDL from IDDM and control subjects both donated TG and CE to HDL₂ and affected little change in HDL₃. These findings indicate that all the major plasma fractions normally participate in the trafficking of CE and TG among the lipoproteins during neutral lipid transfer and show that the principal perturbation in cholesteryl ester transfer in IDDM involves altered interaction between VLDL and the HDL₃ subfraction.