OBJECTIVE

To investigate the effects of medroxyprogesterone acetate (MPA) on the beneficial effects of estrogen therapy on lipid metabolism in postmenopausal women.

METHODS

Postmenopausal women were administered either conjugated equine estrogen (CEE) 0.625 mg daily for 3 months (Group 1) or CEE 0.625 mg in conjunction with MPA 2.5 mg (Group 2) or MPA 5.0 mg (Group 3) daily for 3 months. Plasma levels of cholesterol, triglyceride, lipoprotein lipids, apolipoproteins, sex steroid hormones and lecithin cholesterol acyltransferase activity (LCAT) were determined. Lipoprotein lipase (LPL) and hepatic triglyceride lipase (H-TGL) activities were measured in postheparin plasma. Changes in the lipid concentrations and enzymatic activities were evaluated in each group.

RESULTS

Total, low-density lipoprotein (LDL) cholesterol, apolipoprotein B concentrations and LCAT activity were all significantly reduced by treatment in the three groups. The levels of high-density lipoprotein (HDL), HDL2, and HDL3 cholesterol as well as the levels of apolipoprotein AI and AII were significantly elevated in groups 1 and 2. The mean decrease in these parameters was related to the dose of MPA. Levels of triglyceride in the HDL and HDL2 were significantly increased in group 1. The levels of triglyceride in plasma, very low density lipoprotein (VLDL), LDL, HDL3 and VLDL cholesterol and LPL activity were unaffected. H-TGL activity was significantly inhibited only in groups 1 and 2. MPA produced a dose-dependent increase in H-TGL activity. A significant negative correlation was observed between the HDL cholesterol concentration and H-TGL activity (r = 0.58 P < 0.001).

CONCLUSIONS

The administration of MPA 2.5 mg and 5.0 mg did not adversely affect the changes in VLDL-LDL metabolism produced by estrogen. However, MPA has dose-dependent negative effects on HDL metabolism by increasing H-TGL activity and the 5.0 mg MPA interferes with the favorable effects on lipids of estrogen in postmenopausal women.

1. Plasma lipoprotein metabolism and body composition in lines of chicken selected for high- and low-plasma very low density lipoprotein (VLDL) concentrations were compared to the commercial broiler (meat-type) line from which they were derived. 2. Selection for low-plasma VLDL concentration for 10 generations has reduced the rate of VLDL secretion by at least 50% in males whereas selection for high-VLDL concentration has increased the rate of VLDL secretion over 2-fold. 3. Body fat content was highly correlated with rate of secretion of plasma triglyceride-rich (TGR) lipoproteins (r = 0.88 over the three lines). However, extrapolation of the data suggests that birds secreting no TGR-lipoproteins into the plasma would still have substantial amounts of body fat. 4. Selection for high VLDL has increased the proportion of circulating VLDL-triglyceride taken up by the abdominal fat pad by over 2-fold but there was no difference between high- and low-VLDL lines in the proportion of VLDL-triglyceride taken up by tissues and oxidised to [14C]-carbon dioxide. 5. The results confirm the importance of plasma lipoprotein metabolism in determining body composition in the chicken but suggest there are limits to further reduction in body fat content by manipulation of plasma lipoprotein metabolism.

A method is described for the determination of VLDL apolipoprotein B by radial immunodiffusion (RID) in serum supernatants following precipitation of LDL with polyvinylsulphate. The measurement of VLDL apolipoprotein B is based on the incubation of the polyvinylsulphate supernatant with triglyceride lipase (330 kU/l end concentration) for 12-24 hours at 37 degrees C. A good measure of agreement was found for the corresponding VLDL apolipoprotein B values measured by RID in the polyvinylsulphate supernatants (y) and VLDL apolipoprotein B values calculated as tetramethylurea-insoluble protein in the d less than 1.006 kg/l serum fraction (x) (r = 0.88, y = 0.96x + 0.004, n = 54). Within the tested range of 1.2 mmol/l to 6.7 mmol/l triglycerides, the concentration of apolipoprotein B measured in the polyvinylsulphate supernatant showed a linear relationship. Correlation analysis of VLDL apolipoprotein B values and serum triglycerides and VLDL cholesterol, respectively, showed a good correlation (r = 0.77 and r = 0.75, respectively, n = 54). In the determination of VLDL apolipoprotein B measured in polyvinylsulphate supernatant, a variation coefficient of 4.3% (means = 10.1 mmol/l, n = 20) was found in relation to the precision in the series, and a variation coefficient of 11.4% (means = 5.3 mmol/l, n = 15) in relation to day to day precision.

Alterations in the relative proportions of very low density lipoprotein (VLDL) apoprotein C-III (apoC-III) isoforms have been previously observed under various dietary and metabolic states. This study was designed to evaluate the effects of a very high caloric restriction on plasma triglycerides and on the relative proportions of VLDL apoprotein C-II (apoC-II) and apoC-III isoforms in obese subjects. VLDL were isolated by preparative ultra-centrifugation from 12 obese women. ApoC-II and apoC-III subspecies were separated by analytical ultrathin-layer isoelectrofocusing. The mean body weight decreased significantly from 96.2 +/- 8.7 to 90.6 +/- 7.6 kg (p less than 0.01). Mean total and VLDL triglycerides did not vary significantly. Apoprotein C-III2 (apoC-III2) as percentage of total apoprotein C increased (p less than 0.01) and apoprotein CIII0 (apoC-III0) decreased (p less than 0.01). Apoprotein C-III1 (apoC-III1) did not vary significantly. An inverse correlation was found between the percentage variation of apoC-III2 and that of apoC-III1 (r = -0.94; p less than 0.01). The variations of apoC-III2 correlated positively (r = 0.83; p less than 0.01), while those of apoC-III1 correlated inversely (r = -0.65, p less than 0.025) with the changes of VLDL triglycerides. The apoC-III1 to apoC-III2 ratio as well as the apoC-III0 to apoC-III2 and apo C-III1 ratios decreased after diet (p from less than 0.01 to less than 0.001). Total apoC-III as well as apoC-III2 and apoC-III1 to apoC-II ratios did not vary.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE

To study if the course of cerulein-induced pancreatitis in rats changes in a state of triglyceride-rich lipoprotein metabolism alteration.

METHODS

Two groups of rats received control diet during a 90-day period (A) and sucrose-rich diet to induce endogenous hypertriglyceridemia (B). Subgroups A2 and B2 received i.p. 45 microg cerulein/kg body weight (to induce acute pancreatitis). Histological examination of pancreas tissue, serum pancreatic lipase, lipoprotein profile and VLDL chemical composition were assessed. Then, pancreatic lipase hydrolytic activity on VLDL-triglycerides was evaluated in vitro.

RESULTS

Cellular vacuolization was observed in all of the cerulein-injected rats, but only in subgroup B2 fat necrosis was present. Serum triglycerides were higher in subgroup B1 than in subgroup A1 (mean +/- SEM, mg/dl 123,77 +/- 25.7 vs. 65.8 +/- 7, p < 0.01). Triglycerides from rats fed with sucrose-rich diet, decreased after cerulein-induced pancreatitis (80.38 +/- 11.3 vs. 123,77 +/- 25.7, p < 0.02). Moreover, the endogenous hypertriglyceridemic rats showed an increment of VLDL triglyceride content, which decreased when rats were injected with cerulein. A negative correlation was found between VLDL-triglyceride content and serum pancreatic lipase activity (r = 0.58, p < 0.02). The in vitro assay showed a decrease in VLDL-triglyceride content post incubation with pancreatic lipase enriched serum (mean +/- SD: 59.2 +/- 27.7%, p < 0.01).

CONCLUSIONS

The endogenous hypertriglyceridemia intensifies the course of cerulein-induced pancreatitis and it could be related to the decrease in VLDL-triglycerides as a consequence of pancreatic lipase hydrolytic activity.

The close association between nonalcoholic fatty liver and insulin resistance is now widely recognized. While the former is characterized by excessive intrahepatic triglyceride accumulation, the latter induces overproduction of very-low-density lipoprotein (VLDL) particles. It has not been well elucidated whether these apparently opposite mechanisms impact on VLDL characteristics or not. The aim of the present study was to evaluate the VLDL secretion and features resulting from insulin resistance and fatty liver in rats fed a sucrose-rich diet (SRD, i.e. addition of sucrose to drinking water during 12 weeks). No differences in calorie intake were observed in comparison to controls. Both groups showed similar weight gains throughout the treatment period. However, SRD rats showed an increased proportion of body fat as assessed by X-ray absorptiometry, increased visceral obesity, liver weight and fat accumulation in the liver (p < 0.04). Histological study revealed moderate micro- and macrovesicular steatosis. Fasting insulin, triglyceride and free fatty acid (FFA) levels increased while VLDLs decreased in SRD rats (p < 0.05). The chemical composition of VLDLs of SRD rats showed a higher percentage of triglycerides, and the VLDL triglyceride/protein ratio, an estimator of lipoprotein size, suggests that VLDL particles of SRD rats are larger than those of controls (p < 0.0005). FFA levels correlated with VLDL triglycerides (r = 0.49, p = 0.03) and liver fat content correlated with plasma triglycerides (r = 0.65), VLDL triglycerides (r = 0.55) and triglyceride/protein ratio (r = 0.52, p < 0.02). The VLDL secretion rate assay showed an increase in SRD rats (p < 0.02), confirming an overproduction despite liver fat accumulation. Our findings are consistent with an insulin resistance development model in which hepatic lipid content would constitute an important determinant of a triglyceride-rich, large-particle VLDL secretion; both features would increase its atherogenic potential.

The relationship between low-density lipoprotein (LDL) peak particle diameter and insulin sensitivity, very-low-density lipoprotein (VLDL) + intermediate-density lipoprotein (LDL) triglyceride, cholesterol, and apoprotein B, postprandial lipemia, and LDL + high-density lipoprotein (HDL) triglyceride was assessed. The subjects were 101 healthy males aged 15 to 45 years. Sixty-one subjects (60.4%) were offspring of a parent with coronary artery disease before age 60, and 40 subjects (39.6%) had no parental history of coronary artery disease. LDL peak particle diameter was measured following polyacrylamide gradient gel electrophoresis. An insulin sensitivity index (Si) was determined from a frequently sampled intravenous glucose tolerance test using a minimal modeling method. A fat tolerance test was performed with a test meal containing 70 g/m2 fat, with triglyceride concentrations measured hourly for 12 hours. LDL peak particle diameter was significantly correlated with body mass index (BMI) (r = -.282, P < .01), waist to hip ratio (r = -.291, P < .01), fasting triglyceride (logarithmically [log] transformed) (r = -.566, P < .001), area under the postprandial triglyceride curve (log transformed) (r = -.562, P < .001), VLDL + IDL triglyceride (log transformed) (r = -.462, P < .001), VLDL + IDL cholesterol (log transformed) (r = -.477, P < .001), VLDL + IDL apoprotein B (log transformed) (r = -.321, P < .001), LDL + HDL triglyceride (log transformed) (r = .583, P < .001), and HDL cholesterol (r = .347, P < .001), but there was no significant correlation with Si. Using stepwise regression analysis, LDL + HDL triglyceride showed the strongest relationship to LDL peak particle diameter, accounting for 34% of the variation in size. Si was not an independent predictor of LDL particle size. In conclusion, insulin sensitivity appears to have little influence on LDL particle size. The importance of LDL + HDL triglyceride should be considered a preliminary finding warranting verification in this and other populations.

We studied the effects of very low density lipoprotein (VDL) obtained from hypertriglyceridemic subjects on the secretion of lipoprotein lipase and lipid accumulation in human monocyte-derived macrophages. The incubation of macrophages with VLDL obtained from different subjects caused different effects on the secretion of lipoprotein lipase (6.8 to 137.7 nM free fatty acid/min/mg cell protein) and triglyceride accumulation (184 to 507 micrograms/mg cell protein) in human monocyte-derived macrophages. VLDL from subjects with marked hypertriglyceridemia (approximately 1000 mg/dl) had a fourfold greater effect on lipoprotein lipase activity and a twofold greater effect on cellular triglyceride accumulation when compared with the effects of VLDL from normolipidemic subjects. Both lipoprotein lipase activity and triglyceride accumulation correlated positively with plasma VLDL triglyceride levels (r = 0.50 and 0.45, respectively, p less than 0.05). From these data, we suggest that the activity of lipoprotein lipase secreted from macrophages incubated with VLDL was dependent on triglyceride concentrations, and that the secretion of lipoprotein lipase enhanced by hypertriglyceridemic VLDL was closely related to the intracellular accumulation of triglyceride.

In 17 patients with primary mixed hyperlipidemia we studied levels and composition of lipoproteins in fasting plasma, lipoprotein-modifying enzymes, and postprandial lipoprotein metabolism after an oral fat-tolerance test supplemented with vitamin A before, and 12 weeks after treatment with etophylline clofibrate. With treatment, fasting plasma cholesterol, triglycerides, and the levels of very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL) decreased significantly; high density lipoprotein (HDL) cholesterol increased significantly. Treatment caused also an increase in the protein content of IDL, a decrease in the triglyceride content of LDL, and an increase in the size of LDL as assessed by gradient gel electrophoresis. Concentrations of triglycerides, chylomicrons, and chylomicron remnants after an oral fat load supplemented with vitamin A decreased by 33%, 30% and 6%, respectively (P < 0.005; P < 0.01; and P < 0.05). The activity of lipoprotein lipase and hepatic lipase in postheparin plasma increased by 51% and 45%, respectively (P < 0.01; P < 0.05). We found a decrease in the mass concentration of cholesteryl ester transfer protein (P < 0.05). Stepwise multiple regression analysis showed that the triglyceride content of LDL is determined primarily by fasting triglycerides (r = + 0.53, P < 0.05;baseline) and cholesteryl ester transfer protein (r = + 0.49, P < 0.05; 12 weeks); in contrast, the triglyceride content of HDL3 is determined exclusively by accumulation of postprandial triglycerides (r = + 0.67; P < 0.05; baseline) and postprandial chylomicrons (r = +0.87; P < 0.005; 12 weeks). We conclude that hypolipidemic treatment with etophylline clofibrate favorably affects the cardiovascular risk factor profile in primary mixed hyperlipidemia.

The Friedewald formula has been widely used in the estimation of the serum LDL cholesterol concentration in diabetic patients. In patients with insulin-dependent diabetes we have compared the serum LDL cholesterol concentrations obtained when VLDL was isolated in the preparative ultracentrifuge and its cholesterol content directly determined with those when the 'Friedewald Formula' assumption that there is a fixed ratio between total serum triglycerides and VLDL cholesterol was used in the calculation of the LDL cholesterol value. Both methods gave similar results which were closely correlated (r = 0.98) with a slope of 0.98 on linear regression analysis for patients with serum triglycerides of less than 2.5 mmol/l. The inclusion of a small number of hypertriglyceridaemic patients (14%) had virtually no impact on these findings.

Very low density lipoprotein (VLDL) 1 and 2 were fractionated by heparin affinity chromatography into a bound and an unbound fraction and the different subfractions were quantified in 17 normolipidaemic (NL), 13 hypercholesterolaemic (HC), 10 hypertriglyceridaemic (HTG) and 11 combined hyperlipidaemic subjects (CHL). Unbound VLDLVLDLre, respectively, 1.9- and 2.2-fold richer in triglycerides than bound VLDLVLDLration of all the VLDL subfractions was increased and plasma triglyceride level was correlated to unbound VLDLVLDLrespectively, r=0.86 (p<0.001) and r=0.77 (p<0.01) in HTG and r=0.73 (p<0.001) and r=0.62 (p<0.05) in CHL). In HC unbound VLDLVLDLration were increased compared to NL and in CHL, the concentration of bound VLDLrticularly increased (3.2-fold compared to NL (p<0.001)). In both HC and CHL bound VLDLration was correlated to low density lipoprotein cholesterol (LDL-C) concentration (respectively, r=0.67 (p<0.01) and r=0.62 (p<0.05)). In hypertriglyceridaemic states the intravascular accumulation of both unbound and bound VLDLrs as the determinant of plasma triglyceride concentration, whereas in moderately hypercholesterolaemic states the concentration of bound VLDLrikingly correlated to LDL-C concentration, suggesting that these two species are linked metabolically, e.g. bound VLDLrecursor pool of LDL.

The effects of long term treatment with nicotinic acid on lipids, lipoproteins, and the plasma distribution of very low density lipoproteins (VLDL) apoprotein C (ApoC) subspecies were studied in 33 patients with types IIa (n = 9), IIb (n = 11), and IV (n = 13) hyperlipidemias. After 6 months of treatment, a significant decrease in triglyceride, total cholesterol, and low density lipoprotein (LDL) cholesterol levels occurred. High density lipoprotein (HDL) cholesterol increased significantly by 31.1%, 41.8%, and 32.0% in types IIa, IIb, and IV, respectively (P less than 0.01 for all). A significant negative correlation existed between changes in HDL cholesterol and triglycerides (r = -0.613; P less than 0.02) in all groups studied. Therapy also produced changes in VLDL, LDL, and HDL protein concentrations. VLDL protein decreased from 20.9 +/- 3.9 to 15.2 +/- 1.0 mg/dl (P less than 0.05) in type IIa. In types IIb and IV, mean VLDL protein decreased from 44.7 +/- 8.2 to 27.1 +/- 3.9 mg/dl (P less than 0.001) and from 46.3 +/- 7.1 to 30.6 +/- 4.9 mg/dl (P less than 0.001), respectively. LDL protein decreased significantly, and HDL protein increased in type IIa only. Gel isoelectric focusing of VLDL before and after nicotinic acid in types IIb and IV hyperlipidemia produced a significant increase in the VLDL ApoC-II component with simultaneous decreases in the total VLDL ApoC-III subspecies. This resulted in increases in the ApoC-II to ApoC-III area ratio from 0.50 +/- 0.1 to 1.02 +/- 0.2 (P less than 0.001) in type IIb and from 0.62 +/- 0.07 to 0.88 +/- 0.13 (P less than 0.01) in type IV, respectively. The ApoE subspecies and the ApoE-III to ApoE-II area ratio did not change significantly. Our results show that nicotinic acid produces a significant improvement in the lipoprotein profiles of these patients.

Menopausal women are at high risk of developing heart disease. However, physical exercise practice can reverse this scenario. We evaluated the biochemical, morphological, and physiological effects of moderate aerobic physical exercise on the pancreas of knockout mice for LDL receptor with estrogen deprivation by ovariectomy. Animals were divided into six groups (n = 5): sedentary non-ovariectomized control; sedentary ovariectomized control; trained ovariectomized control; sedentary non-ovariectomized LDL-R knockout; sedentary ovariectomized LDL-R knockout; and trained ovariectomized LDL-R knockout. Physical exercise practice promoted improvement in biometric and biochemical parameters analyzed, with reduction of visceral adipose tissue and VLDL, triglycerides, total cholesterol, and blood glucose levels. In addition, physical exercise practice altered the morphology of pancreatic islets and improved their response to the effects of menopause. Thus, physical exercise practice was fundamental to minimize the effects of dyslipidemia associated with ovariectomy in the pancreatic tissue of LDL-R knockout animals, contributing to reduce the risk of developing cardiac diseases in the menopause period.

BACKGROUND

The lipid composition of a mammal's spermatozoa and seminal plasma vary in both structure and function. Evidence exists to suggest that dietary supplementation with the appropriate polyunsaturated fatty acids (PUFAs) affects spermatogenesis, semen quality and sperm motility. Therefore, this study has been conducted to evaluate the correlations between serum lipid profile and histological, anatomical and seminal parameters of testes in clinically healthy goats.

METHODS

In this analytic, cross-sectional study, we chose a total of ten mature Iranian male goats that comprised a homogenous group through simple random sampling. Blood samples were taken from the jugular vein; the sera were separated and subsequently used for measurement of serum lipids, lipoproteins and testosterone levels. In addition, we collected semen from the animals and evaluated the seminal characteristics. We also performed histological and anatomical assessments of the testes.

RESULTS

The findings demonstrated that serum levels of high density lipoprotein (HDL-c) had a significant positive correlation with interstitial testicular tissue area (r=0.73; p<0.001), seminiferous tubule area (r=0.61; p<0.01), the number of Leydig cells (r=0.53; p<0.05), the diameter of the Leydig cell nuclei (r=0.54; p<0.05), scrotal circumference (r=0.83; p<0.001), testis weight (r=0.72; p<0.001), the number of live, normal sperm (r=0.94 ; p<0.001) and serum testosterone levels (r=0.88; p<0.001). Significant but negative correlations were found between serum triglyceride concentration and seminiferous tubule area (r=-0.53; p<0.05), the diameter of the Leydig cell nuclei (r=-0.55; p<0.05), testis weight (r =-0.64; p<0.01), total sperm number (r=-0.82; p<0.001), number of live, normal sperm (r=-0.55; p<0.05) and serum testosterone levels (r=-0.79; p<0.001). In addition, a significant negative correlation was observed between serum very low density lipoprotein (VLDL-c) concentration and the percent of live sperm (r=-0.67; p<0.01), and serum testosterone levels (r=-0.65; p<0.01).

CONCLUSIONS

The present results indicated that among serum lipids only the levels of HDL-c positively correlated with testicular parameters. High serum triglyceride levels exerted direct adverse effects at the testicular level, which was mainly observed in the seminiferous tubules (STs), characterization of Leydig cells and semen quality.

Basal plasma total triglyceride and very low density lipoprotein (VLDL) triglyceride turnover rates were determined in 110 subjects whose triglyceride concentrations ranged from low normal to markedly elevated values. The mean total triglyceride turnover rate was 13.7 mg - kg-1- hr-1, whereas the mean VLDL triglyceride turnover rate was 13.2 mg - kg-1 - hr-1. A highly significant correlation was present between the two turnover rates (r equal + 0.75). The endogenous serum triglyceride transported in the other lipoproteins (LDL and HDL) may account for more than half of the circulating triglyceride mass, but its significance in the total triglyceride transport is small. In a selected subgroup of 31 healthy subjects the plasma VLDL triglyceride concentration did not exceed 160 mg/100 ml. The range of this group's triglyceride turnover rate was completely comparable with most data reported in the literature for total serum or VLDL triglyceride transport in normal human subjects. When the turnover rate was plotted against the VLDL triglyceride concentration, three kinetic subgroups could be separated in accordance with the earlier experience on total serum triglyceride transport kinetics.

Nascent high density lipoprotein (HDL) and nascent very low density lipoprotein (VLDL) were isolated from rat livers that had been perfused with [3H]glycerol to label the triglyceride. When injected into intact rats, the labeled HDL-triglyceride disappeared as rapidly as the VLDL-triglyceride, with only 10% of the injected label remaining in the plasma after 30 min. The protein moiety of nascent HDL was labeled with [35S]methionine in a similar fashion and the labeled nascent HDL was separated into nonretained (NR) and retained (R) fractions by heparin-Sepharose affinity chromatography. When injected into rats, 55% of the injected label in nascent fraction NR and 72% of that in nascent fraction R was recovered from plasma at 30 min, compared to only 10% of the triglyceride label from unfractionated nascent HDL, indicating dissociation of triglyceride and apolipoprotein clearance. The plasma decay curves for both triglyceride and protein were biexponential. By 5 min, 15% of the 35S label remaining in plasma represented apoE and apoC that had been transferred from nascent HDL fractions NR and R to the d less than 1.063 g/ml fraction of plasma. Plasma HDL was labeled in vivo with [35S]methionine, separated into fractions NR and R, and the clearance of the two plasma HDL fractions was compared with that of the corresponding nascent HDL fractions. Except for a faster rate of removal of the nascent HDL fractions during the first 5 min, the serum decay curves were very similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma lipoproteins, VLDL triglyceride kinetics, and bile acid and cholesterol synthesis were measured in 21 patients heterozygous for familial hypercholesterolemia with (n = 11) or without (n = 10) ileal bypass. LDL cholesterol and apoprotein B concentrations were lower, and cholesterol and bile acid synthesis, the VLDL triglyceride/cholesterol ratio, and the HDL cholesterol concentration were higher in the operated than the control patients. The VLDL triglyceride production rate was increased in the operated normotriglyceridemic patients by about 65%, whereas the fractional catabolism of VLDL triglycerides and the calculated VLDL cholesterol transport were similar in the operated and control groups. VLDL triglyceride production was not correlated with cholesterol or bile acid synthesis. The VLDL triglyceride concentration was positively correlated with the production and negatively with the fractional catabolism of VLDL triglycerides. In unoperated normotriglyceridemic patients the VLDL triglyceride production was positively correlated with LDL cholesterol (r = 0.69, p less than 0.05), LDL triglyceride (r = 0.84, p less than 0.01) and LDL apoprotein B (r = 0.80, p less than 0.01) concentrations, and with the LDL triglyceride/apoprotein B (r = 0.72, p less than 0.05) and LDL triglyceride/cholesterol (r = 0.68, p less than 0.05) ratios. None of these correlations was significant in the operated patients. We conclude that in heterozygous familial hypercholesterolemia VLDL triglyceride level depends on both VLDL triglyceride synthesis and catabolism, LDL level is proportionate to VLDL triglyceride production in the unoperated patients but not in the patients with ileal bypass, ileal exclusion results in an increase in the production rate of VLDL triglycerides in normotriglyceridemic patients but otherwise VLDL triglyceride production is poorly associated with cholesterol and bile acid synthesis, ileal exclusion may induce hepatic secretion of triglyceride-rich VLDL.

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.

The relationship of VLDL lipid (cholesterol and triglycerides) levels to fasting and postglucose plasma glucose, plasma glucose, insulin, and free fatty acid (FFA) levels were examined in four subgroups of children (n = 311, ages 6 to 18 years) from a total biracial population whose earlier beta- or pre-beta-lipoprotein cholesterol levels (or both) were in the extreme quintiles or quartiles. High beta-lipoprotein cholesterol strata with or without elevated pre-beta-lipoprotein cholesterol showed significantly high levels of FFA and glucose response (mean, 30 and 60 minutes) to oral glucose load, whereas postglucose insulin responses were markedly higher in the high pre-beta-lipoprotein cholesterol strata. VLDL triglycerides related closely with fasting plasma glucose levels (r = 0.53 to 0.60, P less than 0.001) and to a lesser extent with postglucose plasma glucose response (r = 0.37 to 0.44, P less than 0.001) in all cases. For insulin and FFA, however, correlations were significant only in certain subgroups. Similar relationships were noted for VLDL cholesterol. Measurements relating to carbohydrate tolerance, age, and race accounted for 35% to 48% of the variability in VLDL lipid values. Surprisingly, fasting plasma glucose showed the highest partial regression coefficient for VLDL lipid in all subgroups except high pre-beta-lipoprotein cholesterol and low beta-lipoprotein cholesterol category, in which age was the major predictor variable. These results demonstrate that subtle abnormalities in the above-mentioned metabolic interrelationships are established early in life.

We compared sodium phosphotungstic acid and magnesium chloride precipitation method for high-density lipoprotein (HDL) cholesterol quantitation with the ultracentrifugation method in 64 insulin-dependent diabetic patients with plasma triglyceride less than 3 mmol/l. The cholesterol content of HDL after precipitation of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was 86% +/- 3% of the cholesterol content of HDL (q greater than 1.063) determined after ultracentrifugation at q = 1.063 (1.33 +/- 0.05 mmol/l vs 1.55 +/- 0.06 mmol/l; p less than 0.001). HDL cholesterol determined after precipitation closely correlated to HDL cholesterol determined after ultracentrifugation (r = 0.97; p less than 0.001). The absolute difference between the HDL cholesterol values obtained by the two methods was correlated to HDL cholesterol (ultracentrifugation) (r = 0.75; p less than 0.001), but it was not correlated to VLDL cholesterol, LDL cholesterol, triglyceride, HbA1c, blood glucose or serum albumin. LDL cholesterol calculated by use of Friedewald's formula was 108% +/- 4% of the cholesterol content of LDL (q = 1.019 to 1.063), determined after ultracentrifugation, but the calculated and the ultracentrifugally determined LDL cholesterol values were closely correlated (r = 0.98; p less than 0.001). These results suggest that during sodium phosphotungstic acid and magnesium chloride precipitation of plasma from diabetic patients, a constant fraction of HDL cholesterol is co-precipitated, resulting in a systematic difference in HDL cholesterol quantitation when compared with the ultracentrifugation method.

Cholesterol, phospholipid and apoB levels were determined in LDL precipitated by amphiphatic polymers (Biomérieux kit, Marcy-l'Etoile, France). Intra-assay and inter-assay analysis performed on 4 serum pools were satisfactory. For 113 sera (triglyceride level less than 4.5 mmol/l, absence of VLDL-remnants), the 3 variables were well correlated with those of centrifuged LDL (0.93 less than r less than 0.98); however, LDL-cholesterol values were significantly higher (p less than 0.001), and those of LDL-phospholipids (p less than 0.001) and LDL-apoB (p less than 0.005) significantly lower. The correlations between the 3 constituents studied gave statistically different regression coefficients for the two methods. It is concluded that these precipitated lipoproteins do not seem to correspond to LDL but to "LDL markers".

In patients with insulin-dependent diabetes mellitus (IDDM), albuminuria reflects widespread vascular dysfunction. Albuminuria has been associated to defects of heparan sulfate proteoglycan (HSPG) within the extracellular matrix. Our hypothesis is that loss of HSPG in vascular walls reduces the HSPG-bound lipoprotein-lipase activity (LPLA), thereby causing elevated levels of plasma triglyceride (TG) seen in IDDM patients with albuminuria. The aim of the present study was to evaluate whether LPLA in muscle capillaries could be related to TG in IDDM patients with and without albuminuria. This is a cross-sectional study including ten healthy control subjects (group C), nine patients with IDDM and urinary albumin excretion rate (AER) of 30 mg/24 h or less (group D0) and 20 patients with IDDM and AER greater than 30 mg/24 h (group DA). Muscle LPLA, plasma TG, total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and very-low-density lipoprotein cholesterol (VLDL) were measured. Between groups no difference in total cholesterol, TG, VLDL, and LDL was found. In patients with albuminuria, LPLA was reduced compared to controls, however, the difference between the groups was not statistically significant [median (range)] 35.9 mU/g (20.4-103) versus 44.6 mU/g (28.2-57.2) and 40.9 mU/g (21.7-53.5) in group DA, C, and D0, respectively, p = 0.76. AER was not correlated to LPLA. An overall negative correlation between TG and LPLA was found; r = -0.33, p = 0.04, supported by an overall significant positive correlation between LPLA and HDL; r = 0.32, p = 0.045. We conclude that, in insulin-dependent diabetes mellitus, skeletal muscle lipoprotein-lipase activity is associated with plasma triglyceride, while an association between lipoprotein-lipase activity and urinary albumin excretion is questionable.

BACKGROUND

Androgenic obesity is associated with a higher risk of metabolic disorders, thus favoring the occurrence of cardiovascular diseases and other morbidities.

OBJECTIVE

To verify the influence of the visceral adipose tissue (VAT) area, measured by computed tomography (CT), on the metabolic alterations in adult and elderly individuals.

METHODS

CT results and lipoprotein levels, total cholesterol and fractions, triglycerides, glycemia and uric acid levels, were obtained from 194 individuals stratified by sex, age group and body mass and analyzed using the tests of correlation and means.

RESULTS

The elderly individuals presented higher VAT area, glycemia, uric acid and total cholesterol levels. The most important correlations were observed between VAT area, triglycerides (TG) and VLDL-c (r>> 0.5; p < 0.01), in both age groups. The mean VAT area was always higher when TG and glycemia levels were altered, in both age groups.

CONCLUSIONS

Most tests showed a strong correlation with VAT area, which was considered as risk for metabolic alterations. In elderly individuals, the risk VAT area seems to be higher than that of adult individuals.

Android obesity is reported to be a risk factor for coronary heart disease and aberrations in lipid metabolism, but so far its association with other risk factors such as age and overweight has not been clearly analyzed. We therefore investigated the relationship between the waist-to-hip ratio, age, body mass index and serum lipoproteins in 305 probands (158 men, 147 women), while body mass index was kept constant in all age groups. Waist-to-hip ratio correlated with both age (r = 0.441) and body mass index (r = 0.532) in simple linear correlation analysis (P less than 0.001). In stepwise multiple regression analysis we found in both sexes a first step dependence on age for total and LDL-cholesterol (P less than 0.001), a first step dependence on waist-to-hip ratio for triglycerides (P less than 0.001), VLDL-triglycerides (P less than 0.001) and VLDL-cholesterol (P less than 0.001 for men, P less than 0.05 for women), and an inverse first step dependence on body mass index for HDL-cholesterol (P less than 0.05 for men, P less than 0.001 for women). From these results we propose an independent association between waist-to-hip ratio and triglycerides while the relation to total and LDL-cholesterol is determined by age. HDL-cholesterol, on the other hand, is influenced by body fat mass and independent from age or body fat distribution.