Changes in the composition and physico-chemical characteristics of serum lipoproteins during ethanol-induced lipaemia in alcoholic subjects.

The effect upon serum lipids and lipoproteins of a large intake of ethanol (180 g in 6 hr) has been studied during the ensuing 24 hr in 21 subjects. These were all men who were habituated to heavy drinking but who were shown to be normolipaemic when maintained on a normal diet with a restricted intake of alcohol. In all the subjects studied, ingestion of this amount of ethanol induced an acute hypertriglyceridaemia which varied in intensity between individuals, with increases ranging from 26% to 377% above the basal value. On the other hand, no significant change occurred in plasma cholesterol. In addition to measurements of triglycerides and cholesterol, the plasma from all the subjects were examined by electrophoresis in agarose and polyacrylamide gels with photometric scanning of the gels. In a subgroup of ten of the subjects, the plasma lipoproteins were separated into very low density (VLDL), low-density (LDL), and high-density (HDL) fractions, which were also analyzed biochemically and by electrophoresis. Following ethanol ingestion, a mean increase of about twofold in triglyceride content, and a decrease in the cholesterol/triglyceride ratio was observed in VLDL, LDL, and HDL. The triglyceride/protein ratio decreased in VLDL and increased in LDL. On electrophoresis of the intact sera following ethanol ingestion visible particulate fat and a band which failed to permeate the gel ('chylomicron-like band') was observed in five out of ten subjects and eight out of these ten subjects showed a prominent prebetalipoprotein (pre-beta) band. This component was found to be present in the lipoprotein fraction of density greater than 1.006 Kg/1. Examination of this fraction from basal specimens revealed a pre-beta band in only two of the ten subjects and the intensity of this band increased in the corresponding fractions from the same subjects after ethanol ingestion. In an additional four subjects no pre-beta was detected in this fraction before ethanol but appeared after ethanol ingestion. No attempt has been made to characterize further the component with these characters but it is suggested that it is probably an intermediate lipoprotein (ILDL), that is, a lipoprotein with characteristics intermediate between VLDL and LDL.     

Quantitative and qualitative serum lipoprotein analysis. Part 2. Studies in male survivors of myocardial infarction.

The fasting concentration of cholesterol and triglycerides in serum and in very low (VLDL), low (LDL) and high (HDL) density lipoproteins (LP) was determined 3 months after a myocardial infarction (MI) in 54 men, and the values obtained were compared to those in 61 healthy male control subjects. The mean triglyceride concentration in MI patients was significantly increased in serum, VLDL, LDL and HDL by 74%, 110%, 30% and 12% respectively, compared to controls. The mean cholesterol concentration was significantly raised by 16%, 120% and 14% in serum, VLDL and LDL but decreased by 22% in HDL. Hypertriglyceridaemia occurred in 58% of MI patients. Of these patients, two-fifths had hypertriglyceridaemia only and three-fifths had combined hyperlipidaemia. The hypertriglyceridaemia was caused by elevation of only VLDL triglycerides in 26%, only LDL triglycerides in 19%, VLDL and LDL triglycerides in 23% and by various other combinations of raised LP triglyceride levels in 25% of cases. Hypercholesterolaemia was found in 41% of MI subjects. Of these, one-sixth had elevation of cholesterol levels, while five-sixths had combined hyperlipidaemia. The LP abnormalities underlying hypercholesterolaemia were increased of only VLDL cholesterol levels in 36%, only LDL cholesterol in 14% and both VLDL and LDL cholesterol in 50% of cases. The low HDL cholesterol values in comparison to controls were related to higher VLDL triglyceride values in MI patients, since HDL cholesterol fell significantly with increasing VLDL triglyceride levels. When HDL cholesterol was related to similar VLDL triglyceride levels, there were no major differences between controls and MI.     

The hypolipidemic action of probucol. Drug transport and lipoprotein composition in type IIa hyperlipoproteinemia

In this study Probucol transport and the effect of the drug on lipoprotein composition in 9 cases of type IIa hypercholesterolemia were investigated. Probucol lowered plasma cholesterol by 20%, without affecting triglycerides. HDL cholesterol was decreased and a slight reduction in LDL cholesterol was noted. This was due to a reduction in the number of circulating lipoprotein particles, without modification in the lipid/protein ratio, mainly cholesterol/protein ratio. Probucol was almost entirely removed by lipoproteins; 75% of the drug was found in LDL, the remainder being equally distributed in VLDL and HDL. There was no correlation between the serum Probucol level, or the amount of Probucol bound to lipoproteins, and the decrease in serum or lipoprotein cholesterol. However, there was a significant increase of the EC/TC (esterified cholesterol/total cholesterol) ratio in VLDL and LDL, but not in HDL.     

Serum lipoproteins and apolipoproteins in young male survivors of myocardial infarction

Concentrations of serum lipoprotein lipids and apolipoproteins A-I, A-II and B were determined 3-6 months after myocardial infarction in 116 males below the age of 45 and in 116 age-matched controls. Among single variables the sum of cholesterol concentration in VLDL and LDL divided by the HDL cholesterol level was the best discriminator between patients and controls. The concentrations of serum triglycerides, apolipoprotein B, VLDL triglycerides and cholesterol, serum cholesterol, HDL cholesterol and LDL triglycerides, in that order, were better discriminators than was LDL cholesterol level. Among variables reflecting HDL concentration and composition HDL cholesterol was the best discriminator followed by HDL2 cholesterol, apolipoprotein A-I and the HDL cholesterol/apolipoprotein A-I ratio. Multivariate analysis indicated independent significance of elevated VLDL lipid and LDL cholesterol concentrations, and a decreased HDL cholesterol concentration, in relation to MI. The present data suggest that a disturbed triglyceride metabolism, in addition to elevated LDL and decreased HDL cholesterol levels, has an independent and pathogenetic significance for MI at a young age.     

Hyperlipemia and arteriosclerotic cardiovascular disease in the Polynesian population of Rarotonga

Total cholesterol, total triglyceride and high density lipoprotein (HDL) cholesterol and their relation to arteriosclerotic cardiovascular disease (ASCVD) were investigated in a population of Polynesian Maoris in Rarotonga who are becoming increasingly westernized. 8.5% of the population had plasma triglyceride elevations (triglyceride greater than or equal to 200 mg/dl), and the occurrence of hypertriglyceridemia was significantly higher in males than females. 5.8% of the population had elevations of total cholesterol (cholesterol greater than or equal to 250 mg/dl), and the proportion with elevation of total cholesterol was similar for males and females. 3.2% of the population had elevations of both triglyceride and cholesterol. HDL cholesterol concentrations were relatively low, and no sex differences were observed at any age. Analysis of lipoprotein cholesterol and triglyceride in a subset of those who had hyperlipemia indicated that the elevations of total cholesterol and triglyceride were mainly due to elevations of low density lipoprotein (LDL) cholesterol and very low density lipoprotein (VLDL) triglyceride, respectively; furthermore, elevations of VLDL triglyceride and LDL cholesterol were significantly correlated with increase in VLDL apolipoprotein B (apo B) and LDL apo B, respectively. Although an appreciable prevalence of diabetes was observed in this population (male: 6.7%, female: 8.4%), the diabetes could not account for the hyperlipemia. Among 693 subjects between the ages of 30 and 59 years, approx. 3% of males and 1% of females had Q-wave changes, and 16% of females and 4% of males had ST-T changes. Among males with Q-wave abnormalities, hyperlipemia was more frequent. There was also increased frequency of hypertension in those with elevated lipids. The data indicate the occurrence of some hyperlipemia in this population which could be of the familial-combined type; the elevated plasma lipids may contribute to the increased frequency of coronary heart disease.     

Lipoprotein profile in men with peripheral vascular disease. Role of intermediate density lipoproteins and apoprotein E phenotypes.

BACKGROUND. The role of lipoprotein disturbances in the development of peripheral vascular disease (PVD) has not been sufficiently clarified. METHODS AND RESULTS. The relations among concentrations of intermediate density lipoproteins (IDL), apoprotein (apo) B, apo E, and other lipoproteins were studied in 102 men with PVD and 100 healthy men who formed the control group. Patients with PVD had significantly higher levels of serum triglycerides, very low density lipoprotein (VLDL) cholesterol, VLDL triglycerides, VLDL proteins, IDL cholesterol, and IDL triglycerides and lower levels of high density lipoproteins (HDL) than controls. Serum cholesterol and triglycerides were normal in 30 patients (cholesterol, less than 5.2 mmol/l; triglycerides, less than 2.3 mmol/l), who had significant increases in IDL triglycerides and significant decreases in HDL cholesterol compared with the 47 controls, who had normal cholesterol and triglyceride levels. Patients with more severe distal involvement showed higher cholesterol and triglycerides carried by IDL and a greater reduction in HDL cholesterol. Smoking patients with PVD showed increased VLDL cholesterol and VLDL triglycerides and lower HDL concentrations. Apo E polymorphism in our study population does not differ from that reported for other European populations. Alleles epsilon 2 and epsilon 4 had a major impact on serum triglycerides and VLDL lipids in our patients with PVD. CONCLUSIONS. Lipoprotein disturbances are a major risk factor for PVD. IDL abnormalities play an important role in the development and severity of PVD and should also be considered a vascular risk factor in normocholesterolemic and normotriglyceridemic patients.     

Comparison between the effects of nafarelin and danazol on serum lipids and lipoproteins in patients with endometriosis

The effects of nafarelin (400 micrograms daily; 12 patients) and danazol (600 mg daily; 6 patients) on serum lipoproteins, high density lipoprotein (HDL) subfractions, and apoproteins-A-I and -A-II were studied. Lipoproteins were fractionated by sequential flotation from samples taken before and after 1, 3, and 6 months of treatment as well as 3 months after cessation of medication. Serum concentrations of estradiol, total and free testosterone, androstenedione, and sex hormone-binding globulin were also determined. On nafarelin treatment, serum total HDL and HDL2 cholesterol concentrations increased slightly, but total and low density lipoprotein (LDL) cholesterol levels were unchanged. There was no effect on apoproteins-A-I and -A-II or on total and very low density lipoprotein (VLDL) triglyceride concentrations. During treatment with danazol, the serum levels of total HDL and HDL2 cholesterol showed profound decrease, as did all the components of HDL2, including apoprotein-A-I. Concomitantly, the total mass of LDL was increased by 25%, accounted for by parallel rises in all of the components of LDL. Total and VLDL triglyceride concentrations decreased inconsistently. Both treatments resulted in hypoestrogenism of the same degree. The steep drop in the serum sex hormone-binding globulin level reflected the androgenic effect of danazol, whereas during nafarelin treatment, serum concentrations of testosterone and androstenedione were reduced. This difference in androgenic milieu may well explain the differences in the lipid profiles. We conclude that, regarding lipid effects, nafarelin is a more favorable treatment for endometriosis than is danazol.     

Relationships of low density lipoprotein subfractions to angiographically defined coronary artery disease in young survivors of myocardial infarction.

Low density lipoprotein (LDL) from 36 young post-infarction patients was separated by isopycnic density gradient ultracentrifugation to determine the relationships of plasma levels and chemical composition of different LDL subfractions to the global severity and rate of progression of coronary atherosclerosis assessed by angiography. There were marked elevations of the cholesterol and triglyceride concentrations in the very low density lipoprotein (VLDL) fraction, whereas the high density lipoprotein (HDL) cholesterol level was reduced in the patients compared with 70 healthy population-based controls. Plasma total LDL cholesterol and triglyceride concentrations were similar. The distribution of apolipoprotein B along the LDL density range, viz. the LDL particle distribution, was displaced towards the dense LDL region among the patients compared with 14 healthy normolipidaemic controls. A preponderance of dense LDL particles was associated with elevated plasma VLDL triglyceride concentration. The patients had significantly higher plasma concentrations of lipid and protein in dense LDL (d greater than 1.040 kg/l), while no group differences were found in the light LDL (d less than 1.040 kg/l). However, there were no percentage compositional differences in the light or dense LDL between patients and controls. Among all constituents of lipoprotein fractions and subfractions determined, only the plasma level of triglycerides in both light and dense LDL correlated significantly with the angiographic estimates of global severity and rate of progression of coronary atherosclerosis, respectively. On a percentage composition basis, both light and dense LDL tended to be richer in triglycerides in the subjects with a more severe coronary artery disease. Neither VLDL or HDL, nor LDL cholesterol were associated with the angiographic scores, the plasma LDL triglyceride concentration or the triglyceride enrichment of LDL. Although there is ample experimental evidence that triglyceride-enriched LDL predisposes to atherosclerosis, the LDL associations with coronary lesion severity and progression observed in the present study might not reflect a causal mechanism, but merely mirror the atherogenicity of disturbances affecting the metabolism of triglyceride-rich lipoproteins. Prospective studies of larger groups of unselected patients are needed to corroborate these findings.     

Effect of the combination of methyltestosterone and esterified estrogens compared with esterified estrogens alone on apolipoprotein CIII and other apolipoproteins in very low density, low density, and high density lipoproteins in surgically postmenopausal women

Androgens are known to lower plasma triglycerides, an independent risk factor for coronary heart disease (CHD). Triglycerides are carried in plasma on very low density (VLDL) and low density (LDL) lipoprotein particles. Apolipoprotein CIII (apoCIII), a strong predictor of CHD, impairs the metabolism of VLDL and LDL, contributing to increased triglycerides. The objective of this study was to assess the effect of oral methyltestosterone (2.5 mg/d), added to esterified estrogens (1.25 mg/d), on concentrations of apolipoproteins and lipoproteins, specifically those containing apoCIII, compared with esterified estrogens alone in surgically postmenopausal women. The women in the methyltestosterone plus esterified estrogen group had significant decreases in total triglycerides, apoCI, apoCII, apoCIII, apoE, and high density lipoprotein (HDL) cholesterol compared with those in the esterified estrogen group. The decreases in apoCIII concentrations occurred in VLDL (62%; P = 0.02), LDL (35%; P = 0.001), and HDL (17%; P < 0.0001). There were also decreases in cholesterol and triglycerides concentrations of apoCIII containing LDL, and apoCI concentration of apoCIII containing VLDL. There was no effect on VLDL and LDL particles that did not contain apoCIII or on apoB concentrations. In conclusion, methyltestosterone, when administered to surgically postmenopausal women taking esterified estrogen, has a selective effect to reduce the apoCIII concentration in VLDL and LDL, a predictor of CHD. Methyltestosterone may lower plasma triglycerides through a reduction in apoCIII.     

Accelerated turnover of very low density lipoprotein triglycerides in chronic alcohol users. A possible mechanism for the up-regulation of high density lipoprotein by ethanol

The concentration of high density lipoproteins (HDL) is related to the catabolism of triglyceride-rich lipoproteins. In order to elucidate the mechanisms by which alcohol increases plasma HDL levels we measured the turnover kinetics of very low density lipoprotein (VLDL) triglycerides in 10 alcoholic men without liver disease and in nonalcoholic control men matched for age, weight and plasma VLDL triglyceride level. The study was repeated in the alcoholics after a 2-week abstinence period. The alcoholic men had elevated HDL cholesterol but reduced low density lipoprotein (LDL) cholesterol as compared to the controls. The fractional catabolic rate and the total turnover (production) rate of VLDL triglycerides were both significantly increased (P less than 0.05) in the alcoholic men before abstinence. After withdrawal of alcohol both the synthetic rate and the catabolic rate of VLDL triglycerides returned to normal and the HDL (HDL2 and HDL3) cholesterol fell. The per cent decrease in HDL2 cholesterol during abstinence was positively correlated to the respective fall of VLDL triglyceride fractional catabolic rate (r = +0.51). The results suggest that the absence of hypertriglyceridemia and the elevated levels of HDL in regular alcohol users may be partly based on increased metabolic clearance of VLDL particles and on subsequent accelerated transfer of the VLDL surface components to HDL.     

Effects of castration and testosterone administration on serum lipoproteins and their apoproteins in male spontaneously hypertensive rat

Serum triglyceride and very low density lipoprotein (VLDL) concentrations were higher in male spontaneously hypertensive rat than in male control Wistar Kyoto rat, whereas serum cholesterol, phospholipids, and high density lipoprotein (HDL) concentrations were lower. Castration of hypertensive rats induced an increase in serum cholesterol, phospholipids, and HDL, and a decrease in serum triglyceride and VLDL. The cholesterol content of HDL increased, whereas the triglycerides decreased after gonadectomy of hypertensive rats. These changes in serum lipids and lipoproteins could be reversed by the administration of testosterone. Apolipoprotein E contents in VLDL and HDL of hypertensive rats were low when compared with control rats but rose after castration and could be reduced by testosterone administration. Hypertensive rats accumulated triglycerides and cholesterol in the liver, which resulted in an increase of liver weight. Castration reduced the hepatic lipids as well as liver weight. The effects of castration and testosterone treatment on lipids and lipoproteins were more prominent in spontaneously hypertensive rats than in control rats. These results suggest that testosterone reduces VLDL catabolism which is related to changes of apolipoprotein composition, and that hypertensive rats are more sensitive to testosterone than control rats.     

Effects of pregnancy, postpartum lactation, and oral contraceptive use on the lipoprotein cholesterol/triglyceride ratio

Lipoprotein cholesterol/triglyceride ratio changes have been observed previously with sex hormone use. To determine if the lipoprotein cholesterol/triglyceride ratio is similarly changed by pregnancy and postpartum lactation, we examined pregnant subjects at 36 weeks gestation and the same women at 6 weeks postpartum and compared them to age-matched, nonpregnant women using or not using oral contraceptives. The cholesterol/triglyceride ratios were examined as means and medians and as curvilinear functions of increasing triglyceride concentration. Median ratios did not predict all ratio changes identified graphically. At very-low-density lipoprotein (VLDL) triglyceride concentrations below 40 mg/dL, the VLDL ratio is less than control in oral contraceptive users and further reduced in pregnant women. Above triglyceride concentrations of 40-60 mg/dL, the curves in the three groups are indistinguishable. No effect of lactation is observed. The low-density lipoprotein (LDL) cholesterol/triglyceride ratio is comparably lower in pregnant subjects and oral contraceptive users at all concentrations of lipoprotein triglyceride and again there is no effect of lactation. In high-density lipoprotein (HDL), there is no effect of either pregnancy or oral contraceptive use on the cholesterol/triglyceride ratio, while it is significantly higher with lactation. Postpartum decreases in the VLDL and LDL cholesterol/triglyceride ratio are seen at all lipoprotein concentrations independent of lactation. We conclude that triglyceride enriches VLDL at low concentrations and LDL at all concentrations in pregnancy and with oral contraceptive use, suggesting a common, hormonal mechanism. HDL is enriched with cholesterol during postpartum lactation, consistent with decreased transfer of cholesterol to other lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lipid composition of serum lipoproteins in patients with primary type IIb and type IV hyperlipoproteinemia.

Cholesterol, triglyceride and phospholipid concentrations of VLDL, LDL and HDL were studied in 20 patients with primary type IIb, 25 patients with primary type IV and in 18 controls. Both types are not only characterized by different concentrations of lipoprotein lipids, but also by their different lipid composition. Type IIb had more triglycerides in the LDL, type IV in the LDL and HDL. The HDL cholesterol content of type IV was decreased. The percent phospholipid concentration of HDL was identical in the 3 groups, demonstrating the constant role of this lipid fraction. The lipid relationships between the lipoproteins showed that the LDL/HDL lipid ratio of type IIb exceeded type IV ratio in spite of normal HDL lipid concentration in type IIb.     

Treatment of hypertriglyceridemia by two diets rich either in unsaturated fatty acids or in carbohydrates: effects on lipoprotein subclasses, lipolytic enzymes, lipid transfer proteins, insulin and leptin

BACKGROUND: There is lack of agreement on which dietary regimen is most suitable for treatment of hypertriglyceridemia, especially if high triglyceride concentrations are not due to obesity or alcohol abuse. We compared the effects on blood lipids of a diet high in total and unsaturated fat with a low-fat diet in patients with triglyceride concentrations of > 2.3 mmol/l. METHODS: Nineteen non-obese male outpatients with triglycerides ranging from 2.30 to 9.94 mmol/l received two consecutive diets for 3 weeks each: first a modified high-fat diet (39% total fat, 8% SFA, 15% monounsaturated fatty acids, 1.6% marine n-3 polyunsaturated fatty acids), and then a low-fat diet (total fat 28%, carbohydrates 54%). RESULTS: The high-fat diet significantly decreased triglycerides (-63%), total cholesterol (-22%), VLDL cholesterol (-54%), LDL cholesterol ( 16%), total apoC-III (-27%), apoC-III in apoB containing lipoproteins (apoC-III LpB; -31%) and in HDL (apoC-III nonLpB; -29%), apoE in serum (-33%) and apoB-containing lipoproteins (nonHDL-E; -42%), LpA-I (-16%), insulin (-36%), and leptin (-26%) and significantly increased the means of HDL cholesterol (+8%), LDL size (+6%), lipoprotein lipase (LPL, +11%), hepatic lipase (+13%), and lecithin: cholesterol acyltransferase (LCAT, +2%). The subsequent low-fat diet increased triglycerides (+63%), VLDL cholesterol (+19%), apoC-III (+23%), apoC-III LpB (+44%) apoC-III nonLpB (+17%), apoE (+29%) and nonHDL-E (+43%), and decreased HDL cholesterol (-12%), LPL (-3%), and LCAT (-3%). Changes in triglycerides correlated with changes in LPL activity and insulin levels. CONCLUSIONS: In hypertriglyceridemic patients, a modified diet rich in mono- and n-3 polyunsaturated fatty acids is more effective than a carbohydrate-rich low-fat diet in correcting the atherogenic lipoprotein phenotype.     

Acute effects of cholestyramine on serum lipoprotein concentrations in type II hyperlipoproteinaemia.

Twelve subjects with primary type IIA hyperlipoproteinaemia were treated with cholestyramine under metabolic ward conditions in order to study the timing of effects of different serum lipoprotein classes. After 1 day's treatment changes occurred in all 3 classes, i.e., very low (VLDL), low (LDL) and high (HDL) density lipoprotein classes. VLDL increased abruptly and remained constant during treatment. The ratio of cholesterol/triglycerides decreased suggesting the formation of larger particles. LDL cholesterol decreased continuously suggesting a different mechanism behind this effect than that on VLDL. LDL triglyceride remained constant indicating a relative increase of LDL1. HDL cholesterol decreased while HDL triglycerides increased. All changes made the lipoprotein pattern more "type IV-like". The findings were in agreement with an increased formation of VLDL and an increased flux of lipoprotein through the cascade VLDL-IDL-LDL1-LDL2.     

Abnormalities of composition and of in vitro lipolysis products of human small very low density lipoproteins in hypertriglyceridemia

Small (Sf 20-100) very low density lipoprotein (VLDL) particles were prepared by density gradient ultracentrifugation of plasma from normolipidemic and type IV hypertriglyceridemic post-infarction patients and healthy controls. The small VLDL separated from the plasma of severely hypertriglyceridemic post-infarction patients were found to contain twice the amount of cholesteryl esters per particle, compared with small VLDL from normolipidemic patients and healthy controls. There was a linear increase in the percentage of cholesterol that was esterified in the small VLDL with the serum VLDL triglyceride concentration (r = 0.66). When incubated for two hours with bovine lipoprotein lipase in excess and bovine albumin as a free fatty acid acceptor at one and the same triglyceride concentration in the medium, the end-product isolated by ultracentrifugation varied as a function of the serum VLDL triglyceride level. The amount of glyceride-glycerol recovered after two hours of incubation with lipoprotein lipase was 13.3 +/- 1.3% (mean +/- SEM) of the initial values and did not correlate with the VLDL triglyceride level. With rising serum VLDL triglyceride concentration, the product isolated in the low density lipoprotein (LDL) density region (1.006 less than d less than 1.063 kg/l) contained more total cholesterol and phospholipids. The linear correlation coefficients for these relations were 0.65 and 0.58 for cholesterol and phospholipids respectively. The ratio of total cholesterol to insoluble protein in the LDL density range after lipolysis rose with increasing serum VLDL triglyceride level (r = 0.68). The end-product was further characterized by density gradient ultracentrifugation of the incubate. In vitro LDL derived by lipolysis of normolipidemic small VLDL was denser than in vitro LDL of hypertriglyceridemic small VLDL. A significant relation was found between the percentage of cholesteryl esters of total cholesterol in the substrate and the relative amount of total cholesterol recovered in the LDL density fraction after lipolysis (r = 0.69). We suggest that the enrichment with cholesteryl esters of small VLDL from type IV hypertriglyceridemic patients is caused by lipid transfer from LDL and high density lipoprotein (HDL) and that the change in VLDL particle composition influences the precursor-product relationship to LDL.     

Lipoprotein and apolipoprotein distribution in Zucker rats following an endurance running program

We examined the response to 12 weeks of endurance running of the obese Zucker rat and its lean littermate with regard to changes in serum lipids, lipoproteins and apoproteins. The obese Zucker rat is hyperlipoproteinemic, characterized by elevated serum triglyceride and cholesterol levels primarily associated with the very low density lipoprotein (VLDL) fraction. In lean Zucker rats, training did not affect the concentrations of serum lipids or apolipoproteins. In marked contrast, obese Zucker rats that were trained had significant decreases in serum concentrations of triglycerides, free and esterified cholesterol, and apolipoprotein B compared to their sedentary counterparts. Training obese rats caused an increase in the serum concentration of apolipoprotein E (HDL fraction). In contrast, training did not affect the concentration of Apo E in lean rats. The VLDL fraction was most affected by training obese rats showing marked 50-65% decreases in VLDL triglyceride and VLDL cholesterol. HDL cholesterol was unchanged in lean rats whereas training prompted a 29% increase in obese rats. These data show that exercise training altered the metabolic abnormalities of obese Zucker rats which are responsible for the accumulation in serum of VLDL, lipids and apolipoproteins.     

Sequence of alcohol-induced initial changes in plasma lipoproteins (VLDL and HDL) and lipolytic enzymes in humans

The sequence of alterations in the concentration and composition of different plasma lipoproteins following alcohol intake is not known. We therefore monitored the concentrations of cholesterol, triglycerides, phospholipids, and proteins in the major lipoprotein fractions (VLDL, LDL, HDL2, and HDL3) in ten nonalcoholic healthy male volunteers who were given 5.5 g of alcohol per kilogram of body weight during 21/2 days (a weekend). In addition, lipoprotein lipase activity was measured in post-heparin plasma and in adipose tissue and hepatic lipase activity was measured in post-heparin plasma before and after the experiment. in a separate control experiment, the same subjects received meals and liquids without alcohol. Blood alcohol levels remained below 1.5 g/L. Alcohol caused a progressive increase in the fasting VLDL triglyceride and phospholipid concentrations, both of which were doubled during the experiment (P less than 0.001). In contrast, the VLDL cholesterol levels remained unchanged until the third morning, when there was a slight increase. The LDL triglyceride and phospholipid concentrations also rose without simultaneous changes in the LDL cholesterol concentration. Consistent with these changes, the HDL cholesterol concentration showed no response to alcohol during the experiment, but the HDL phospholipid level rose from 76 to 99 mg/dL (P less than 0.001). This was reflected as an increase in the HDL2 concentration from 124 to 158 mg/dL (P less than 0.01), whereas no change occurred in the HDL3 level. The increment of HDL2 concentration was due to a rise of its triglycerides, phospholipids, and apoproteins A-I and A-II but not to a rise of cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Close correlation between high-density lipoprotein and triglycerides in normotriglyceridaemia.

The relationship between high-density-lipoprotein (HDL) particle size subclasses and the levels of the major lipoprotein lipids was studied in 74 men consecutively referred to the lipid clinic. HDL (density 1.070-1.21 kg l-1) was separated by polyacrylamide gradient gel electrophoresis (GGE) into five size-defined subclasses, in order of decreasing size as follows: HDL2b, HDL2a, HDL3a, HDL3b and HDL3c. Cholesterol and triglyceride concentrations in very-low-density (VLDL), low-density (LDL) and high-density (HDL) lipoproteins were determined. The level of VLDL triglycerides was negatively correlated with HDL2b (r = -0.66, P less than 0.0001), and positively correlated with HDL3b concentrations (r = 0.65, P less than 0.0001). Both correlations were restricted to subjects with VLDL triglyceride concentrations of less than 1.80 mmol l-1, i.e. those with normotriglyceridaemia. Patients with a history of myocardial infarction and/or angina pectoris (n = 18) had significantly lower HDL2b levels than subjects with asymptomatic hyperlipidaemia (n = 50), i.e. 0.16 vs. 0.22 mg protein ml-1 (P less than 0.05), despite essentially similar cholesterol and triglyceride levels in the VLDL, LDL and HDL fractions, including HDL2 and HDL3 cholesterol.     

Intermediate density lipoprotein levels are strong predictors of the extent of aortic atherosclerosis in the St. Thomas's Hospital rabbit strain

This study assessed nonfasting cholesterol and triglyceride in plasma and in lipoproteins as predictors of the extent of aortic atherosclerosis in 2 similar groups of rabbits from the St. Thomas's Hospital strain; the lipoprotein classes studied in the 2 groups were very low (VLDL), intermediate (IDL), low (LDL), and high density lipoprotein (HDL), and Sf greater than 60 lipoprotein, Sf 12-60 lipoprotein, LDL and HDL, respectively. These rabbits exhibit elevated plasma levels of VLDL, IDL, and LDL, with plasma cholesterol and triglyceride of up to 23 mmol/l and 7 mmol/l, respectively, and with up to 100% of the aortic intima bearing atherosclerosis-like lesions. In group 1 rabbits (n = 25), univariate linear regression showed that cholesterol in plasma, LDL, IDL and in VLDL each were positively associated with the extent of aortic atherosclerosis. In group 2 rabbits (n = 20), cholesterol in plasma, LDL and Sf 12-60, but not in Sf greater than 60 lipoprotein, was consistently positively associated with the extent of aortic atherosclerosis. Neither plasma triglyceride, triglyceride in lipoprotein fractions nor HDL cholesterol was associated consistently with the extent of atherosclerosis. Using step-up multiple linear regression among lipoprotein lipids, IDL and Sf 12-60 lipoprotein cholesterol were the most powerful independent predictors of the extent of aortic atherosclerosis in the 2 groups of rabbits. LDL cholesterol was the only other independent predictor. The results suggest that remnant lipoproteins, whether defined as IDL or Sf 12-60 lipoprotein, play an important causal role in atherosclerosis under conditions where plasma levels of these lipoproteins are elevated.