Patients with Refsum disease accumulate significant quantities of phytanic acid in adipose and neural tissue. The accumulation can be reversed by following a diet low in phytanic acid, yet the mechanism of transport of this fatty acid is obscure. We investigated the distribution of phytanic acid in different lipoprotein subfractions in 11 patients with Refsum disease and 9 unaffected siblings. Plasma phytanic acid was distributed on VLDL (16.2% +/- 12.2%), IDL (1.77% +/- 1.64%), LDL (34.8% +/- 12.6%) and HDL (14.3% +/- 7.87%). No correlations with any parameter were seen with total phytanic acid content. Weak nonsignificant correlations were found with the fractional distribution of phytanic acid and VLDL triglyceride (r = 0.35; p = 0.12) and plasma HDL-cholesterol (r = 0.32; p = 0.16) and with LDL:HDL cholesterol ratio (r = 0.33; p = 0.14). Significant correlation of the fractional distribution of phytanic acid on lipoprotein particles was noted with the ratio of apolipoprotein B: apolipoprotein A1-containing particles (r = 0.46; p = 0.03) and apolipoprotein B: apolipoprotein A1 in HDL2 (r = 0.53; p = 0.01). This suggests that the import-export balance for phytanic acid in plasma is related to forward and reverse cholesterol transport on lipoprotein particles, and only weakly to plasma cholesterol and triglycerides. These ratios of apolipoprotein particles may play a significant role in determining the rate of phytanic acid elimination in patients with Refsum disease.

OBJECTIVE

The authors asked whether polymorphic variation at three genes related to vascular disease, and other vascular disease risk factors, determine late-life depression.

METHODS

A group of 370 participants, representing 57% of survivors of an initial cohort of 1,083 participants in the Medical Research Council treatment trial of hypertension in older adults, had been screened for depression at baseline and were traced and genotyped for genetic analysis 11 years later. Genetic analyses were performed to establish variability at three polymorphisms related to vascular disease: APOE encoding for apolipoprotein-E, VLDL-R encoding for the VLDL cholesterol-receptor, and DCP-1 encoding for angiotensin-converter enzyme. Information on vascular disease and its risk factors (ECG ischemia or arrhythmia, body mass index, serum cholesterol, smoking status, and systolic/diastolic blood pressure) and cognitive functioning was also available from baseline.

RESULTS

The authors found no association between the three studied polymorphisms and depression. Female gender, higher diastolic blood pressure, poorer cognitive functioning, and smoking status at baseline were all associated with depression independently of antidepressant and NSAIDs use, age, ECG-established vascular disease, and the remaining vascular disease risk factors studied.

CONCLUSIONS

This study found no association between late-life depression and three polymorphisms related to vascular disease. Depression was found to independently associated with smoking, female gender, poorer cognitive functioning, and higher diastolic blood pressure. Taken together, this study does not seem to support the notion of a specific link between the studied vascular risk factors or these vascular-related loci and late-life depression.

The epsilon4 allele of the apolipoprotein E gene (APOE) constitutes a major genetic susceptibility factor for Alzheimer disease (AD). Recently, a polymorphic triplet (CGG) in the very low density lipoprotein receptor (VLDL-R) gene, coding for a receptor binding only apoE-containing lipoproteins, was associated with AD in a Japanese population but not in Caucasian American populations. We explored this association and the potential interaction with the APOE polymorphism in a Caucasian sample of sporadic AD and control subjects of similar ages of European origin. The allelic distribution of the VLDL-R polymorphism differed significantly between Japanese and Caucasian populations (p < 0.0001). However, in our population, the presence of at least one VLDL-R 5 repeat allele increased significantly (p < 0.0003) the probability to develop AD after 65 years of age in APOE epsilon4 allele bearers.

Lipoprotein fractions in Rana esculenta were separated using the same salt intervals currently applied for human lipoproteins. Very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) were analyzed with reference to the electrophoretic pattern. The lipoprotein electrophoretic pattern in males and females throughout the reproductive cycle showed minor differences. In general, each fraction was characterized by a specific apolipoprotein content. VLDL and LDL fractions were dominated by a high molecular weight (MW) band, most likely the counterpart of human Apolipoprotein B (apo B). The apo B in R. esculenta cross reacted, although weakly, with antibodies raised against chicken apo B. The HDL fraction showed a band with an apparent MW of 29 kDa. The electrophoretic mobility of the protein moiety of HDL was similar to human apolipoprotein A-I (apo A-I). However, HDL apolipoprotein of R. esculenta did not cross react with antibodies against chicken apo A-I under either denaturing or native conditions. The HDL apolipoprotein of R. esculenta was purified by DEAE-Sephacel chromatography followed by HPLC. Its amino acid composition showed a moderate correlation with trout, salmon, chicken and human apo A-I.

ApoA-II is a major apolipoprotein constituent of high density lipoproteins (HDL) and may play an important role in lipoprotein metabolism and predisposition to atherosclerosis. Previous radiotracer kinetic studies have suggested that the metabolism of apoA-II in humans may be different than the metabolism of apoA-I, the major HDL apolipoprotein. In the present study, we have used an endogenous labeling technique using stable isotopically labeled amino acids to study apoA-II metabolism and compared the results to those obtained by a simultaneous exogenous radiotracer labeling method. Seven subjects with HDL cholesterol levels ranging from 9 to 93 mg/dl and apoA-II levels from 13 to 60 mg/dl were investigated in this study. [13C6]phenylalanine and 131I-labeled apoA-II were simultaneously administered as a primed-constant infusion and a bolus injection, respectively. In the endogenous labeling study, plateau tracer/tracee ratios of VLDL apoB-100 were used as estimates for the precursor pool tracer/tracee ratios for apoA-II synthesis. Residence times of apoA-II using these two independent methods were found to be highly correlated (r = 0.973, P < 0.0002). These results indicate that the endogenous labeling of apoA-II using stable isotopically labeled amino acids is a reasonable alternative to the conventional exogenous radiotracer labeling method for the investigation of apoA-II turnover. However, under the conditions of our experimental design and modeling strategy, the apoA-II residence times as determined by endogenous labeling were significantly longer (mean 5.33 days) than by exogenous radiotracer (mean 4.65 days). This suggests that apoA-II turnover may be even slower than believed based on radiotracer studies, and further supports the concept that HDL containing apoA-II are metabolized differently than HDL without apoA-II.

BACKGROUND

This study investigated the effects of salmonella infection and its chemotherapy on lipid metabolism in tissues of rats infected orally with Salmonella typhimurium and treated intraperitoneally with pefloxacin and amoxillin.

METHODS

Animals were infected with Salmonella enterica serovar Typhimurium strain TA 98. After salmonellosis was confirmed, they were divided into 7 groups of 5 animals each. While one group served as infected control group, three groups were treated with amoxillin (7.14 mg/kg body weight, 8 hourly) and the remaining three groups with pefloxacin (5.71 mg/kg body weight, 12 hourly) for 5 and 10 days respectively. Uninfected control animals received 0.1 ml of vehicle. Rats were sacrificed 24h after 5 and 10 days of antibiotic treatment and 5 days after discontinuation of antibiotic treatment. Their corresponding controls were also sacrificed at the same time point. Blood and tissue lipids were then evaluated.

RESULTS

Salmonella infection resulted in dyslipidemia characterised by increased concentrations of free fatty acids (FFA) in plasma and erythrocyte, as well as enhanced cholesterogenesis, hypertriglyceridemia and phospholipidosis in plasma, low density lipoprotein-very low density lipoprotein (LDL-VLDL), erythrocytes, erythrocyte ghost and the organs. The antibiotics reversed the dyslipidemia but not totally. A significant correlation was observed between fecal bacterial load and plasma cholesterol (r=0.456, p<0.01), plasma triacyglycerols (r=0.485, p<0.01), plasma phospholipid (r=0.414, p<0.05), plasma free fatty acids (r=0.485, p<0.01), liver phospholipid (r=0.459, p<0.01) and brain phospholipid (r=0.343, p<0.05).

CONCLUSIONS

The findings of this study suggest that salmonella infection in rats and its therapy with pefloxacin and amoxillin perturb lipid metabolism and this perturbation is characterised by cholesterogenesis.

The clinical usefulness of cyclosporine is hampered by dose-limiting toxicities to the kidney that are not predicted by drug levels in serum or whole blood. Because of its lipophilic nature, circulating plasma lipoproteins may play a role in drug disposition. This study characterized the pharmacokinetic parameters of a single 2-mg/kg i.v. infusion of cyclosporine in the whole blood, plasma, high-density (HDL), low-density (LDL), and very low-density (VLDL) lipoprotein fractions of nine patients before bone marrow transplantation. The dose- and protein-corrected area under the concentration-time curve in whole blood; plasma; and HDL, LDL, and VLDL compartments were 44.6 +/- 11.3, 19.2 +/- 2.4; 33.6 +/- 12.3, 49.0 +/- 19.9, and 17.5 +/- 9.0 ng h/ml, respectively. The mean half-life of the drug from the VLDL fraction was significantly less than from the other biologic fluids. The systemic clearance rate of cyclosporine was greater in the total plasma or VLDL fractions compared with whole blood and the HDL and LDL fractions. The HDL-cyclosporine clearance inversely correlated with the serum creatinine (r = -0.71; p less than 0.05) and total bilirubin levels (r = -0.76; p less than 0.05). The plasma half-life and volume of distribution directly correlated with fasting HDL cholesterol levels (r = 0.94 and 0.99; p less than 0.01). Correlations between pharmacokinetic parameters and lipid fractions suggest a role of lipids in the distribution of cyclosporine. These data may be useful in the development of guidelines for therapeutic drug monitoring of cyclosporine in the transplantation population.

BACKGROUND

Physical activity and high aerobic fitness protects against cardiovascular disease and early death, besides having a very modest impact on lipoprotein-cholesterol in obese subjects. Physical activity has been shown to favourably alter lipoprotein particle concentrations and apolipoprotein B with minimal weight loss in overweight to moderately obese subjects.

CONCLUSIONS

We studied the impact of physical activity on lipoprotein subclass particle concentrations in women with severe obesity. Increased physical activity duration was associated with favourable changes, whereas increased PA intensity was associated with adverse changes in some lipoprotein particle subclasses in severely obese women. Severely obese women that manage to increase their physical activity level can improve their lipoprotein profile, whether or not they lose fat mass Physical activity (PA) and high aerobic fitness protects against cardiovascular disease and early death possibly among others because of an anti-atherogenic impact on lipoprotein particle concentrations. The objective of this study was to determine the impact of PA and diet on lipoprotein particle concentrations. Thirty-one severely obese women (age 43.6 ± 10.2 years; body mass index 43.0 ± 6.3 kg m(-2) ) participated in a 1-year lifestyle intervention with repeated measurements of lipoprotein particle subclass concentrations and size of very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL), as well as fat mass, PA and diet. Multiple regression was used to determine associations with change (Δ) in two principal components (PCs) describing lipoprotein distributions: ΔPC 1 LIPO (dominated by VLDL and LDL) and ΔPC 2 LIPO (dominated by large HDL and mean HDL particle size). ΔPA duration was the only variable that was significantly related to ΔPC 1 LIPO (partial r = -0.40, P = 0.008), while ΔPA intensity was the only variable that was significantly related to ΔPC 2 LIPO (partial r = -0.43, P = 0.003) in adjusted models. Increased PA duration was associated with favourable changes, whereas increased PA intensity was associated with adverse changes in some lipoprotein particle subclasses in severely obese women.

We examined the association between the kinetics of very-low-density lipoprotein (VLDL) apolipoprotein B-100 (apoB) and intraperitoneal, retroperitoneal, subcutaneous abdominal, and total adipose tissue masses (IPATM, RPATM, SAATM, TATM, respectively) in 14 healthy, non-obese men (body mass index [BMI] < 30 kg/m(2)). Hepatic secretion of VLDL-apoB was measured using an intravenous infusion of 1-[(13)C]-leucine. Isotopic enrichment of VLDL-apoB was measured using gas chromatography-mass-spectrometry and a multicompartmental model (Simulation, Analysis, and Modeling Software [SAAM II]) used to estimate the fractional catabolic rate (FCR) of VLDL-apoB. IPATM, RPATM, and SAATM (kg) were quantified between T11 and S1 using magnetic resonance imaging (MRI); TATM (kg) was determined using bioelectrical impedance. Insulin resistance was estimated by homeostasis model assessment (HOMA) score. In stepwise regression analysis, IPATM was the best predictor of the hepatic secretion of VLDL-apoB (r =.58, P <.05) and TATM the best predictor of the FCR of VLDL-apoB (r = -.56, P <.05). After adjusting for TATM, IPATM explained 59% of the variance in VLDL apoB secretion (P =.03). None of the fat compartments were significantly associated with VLDL-apoB kinetics after adjusting for HOMA score. The findings suggest that in non-obese men the quantity of both intraperitoneal and total fat are significant predictors for the kinetics of VLDL-apoB, which in turn, determines plasma triglyceride concentrations; these associations may, in part, be mediated by variations in insulin resistance, particularly among individual who are not ostensibly obese. Our preliminary results need confirmation in a larger study.

OBJECTIVE

Enhanced fatty-acid desaturation by stearoyl-CoA desaturase enzyme-1 (SCD1) is associated with obesity. This study determined desaturation in the cord plasma of newborns of mothers with and without gestational diabetes (GDM).

METHODS

Newborns of mothers with GDM (n=21) and without (control, n=22) were recruited. Cord plasma fatty-acid desaturation indices (palmitoleic/palmitic, oleic/stearic ratios) were compared, and correlated with anthropometrics and biochemical measures. A subset of very low-density lipoprotein (VLDL) desaturation indices were determined to approximate the liver SCD1 activity.

RESULTS

The total oleic/stearic index was higher in GDM, despite adjustment for cord glucose concentrations. Among GDM and controls, the oleic/stearic index correlated with cord glucose concentrations (rs=0.36, P=0.02). Both palmitoleic/palmitic and oleic/stearic indices correlated with waist circumference (r=0.47, P=0.001; r=0.37, P=0.01). The VLDL oleic/stearic index was higher in GDM.

CONCLUSIONS

The elevated total oleic/stearic index suggests increased lipogenesis in GDM newborns. Factors in addition to glucose supply may influence fetal SCD1 activity.

A cross-sectional study of 130 Bengalee Hindu men (mean age = 50.3 years; SD = 10.5 years) was undertaken to investigate the relationship of body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR) with total cholesterol (TC), high density (HDL-C), low density (LDL-C) and very low-density (VLDL-C) lipoprotein cholesterol, fasting plasma glucose (FPG) and triglycerides (FTG). Correlation studies revealed that WHR was significantly correlated (r = 0.245, p < 0.01) with TC. WC and WHR had significant correlations with VLDL-C, FPG and FTG. All subjects were further divided into two groups based on WHR < or = 0.95 (centrally non-obese, CNO) and WHR>> 0.95 (centrally obese, CO) following the US Joint National Committee (JNC) guidelines. Students' t-test revealed that CO subjects (n = 83) had a significantly higher mean TC (p < 0.05), VLDL (p < 0.05), FPG (p < 0.01) and FTG (p < 0.05) compared with CNO individuals (n = 47). Results of analysis of variance (ANOVA) of central obesity status (CNO = no, CO = yes) and BMI (BMI tertiles used as a categorical variable) with these metabolic variables revealed that CO status had a significant effect (p < 0.05) on TC, VLDL-C, FPG and FTG. BMI tertiles did not a have significant effect on any of these metabolic variables. There was no significant BMI tertile-central obesity status interaction. It can therefore be concluded that the JNC guidelines of WHR>> 0.95 to define central obesity can be used, irrespective of BMI, among this population, to identify individuals who have enhanced metabolic risk factors of coronary heart disease (CHD). Furthermore, it can be routinely used for health promotion purposes among Bengalee men.

We aimed to determine whether the administration of statins to type 2 diabetics without pre-existing CHD reduced the incidence of CHD and their effects on cholesterol and CRP levels. All the participants were carefully interviewed, clinically examined, and laboratory tested to exclude conditions likely to provoke an inflammatory response that was an exclusion criterion.

METHODS

Serious heart, liver or kidney problems, history of renal transplant, recent history of drug or alcohol abuse, HbA1c>10%, blood pressure >140/90 mmHg, BMI >35 kg/m2, triglycerides >3,0 mmol/dm3. 95 obese diabetics (mean age 60,9 years and BMI=31,59 kg/m2, diabetes duration more than 10 years) without pre-existing CHD, were included in the analysis and were randomized to simvastatin (25 female and 20 male used 40 mg simvastatin daily) or placebo (30 female and 20 male) group. After six months, simvastatin significantly lowered CRP levels by 19%, (p<0,01), cholesterol levels by 18%, TG levels by 8%, LDL levels by 20% and VLDL levels by 17%, whereas there was no change with placebo. After one year the difference sustained between groups. Coronary events were rarely in the simvastatin group (6,6%) than in the placebo group (14%). Coronary revascularizations were 4 in the placebo group and 1 in the simvastatin group. Rate of stroke was more often in the placebo group (18%) than in the simvastatin group (8,8%). So, reduction of acute CHD events is for 7,4% in the simvastatin group. Positive correlation was between CRP and CVD (r=0,29). Statin therapy reduced the risk of coronary heart disease in diabetics without CHD.

In 26 type 2 diabetic patients with failure to diet and sulphonylureas (fasting blood glucose levels greater than 8.0 mmol/l) the effects of insulin therapy on blood glucose control, islet B-cell function and plasma lipids were studied. Age was 58 +/- 11 (SD) yr, median duration of diabetes 6.5, range 1-24 yr, and body mass index 24.5, range 18.9-36.3 kg/m2. Six patients were obese. Therapy comprised twice daily injections of intermediate-acting insulin with additional fast-acting insulin when necessary. After six months, insulin dose was 39 +/- 10 U in the non-obese patients. Their fasting (14.0 +/- 2.7 mmol/l) and post-prandial blood glucose (17.9 +/- 4.5 mmol/l) and glycosylated haemoglobin (HbA1, 13.0 +/- 2.0%) declined to 7.7 +/- 1.6 mmol/l, 10.6 +/- 2.6 mmol/l and 9.5 +/- 1.0%, respectively (p less than 0.001). Median body weight increased by 3.7 kg (p less than 0.001). The changes in body weight correlated well with the changes in fasting blood glucose (r = -0.75, p less than 0.01) and HbA1 (r = -0.73, p less than 0.01). Fasting plasma insulin increased (p less than 0.01), whereas fasting plasma C-peptide and C-peptide release after glucagon did not change. Free fatty acids, LDL-cholesterol, total and VLDL-triglycerides showed a significant (p less than 0.05) decrease during insulin treatment. In the six obese patients insulin dose after six months was 44 +/- 18 U. Fasting blood glucose fell from 11.3 +/- 2.2 to 8.8 +/- 2.7 mmol/l (p less than 0.01), and HbA1 decreased from 10.7 +/- 1.1% to 9.8 +/- 1.3% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND

Hypertension and obesity are common problems among diabetic patients accelerating progression of vascular diabetic complications.

METHODS

A two-stage stratified random sampling design was used, and individuals aged 15 years and over were interviewed. This cross-sectional study evaluated lipid abnormalities of 117 obese type 2 diabetic patients (28 males and 89 females), and 56 hypertensive obese type 2 diabetic patients (22 males and 34 females). Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C) and high-density lipoprotein cholesterol (HDL-C) concentrations were assayed using standard biochemical methods.

RESULTS

Hypertensive obese type 2 diabetic females had significantly higher mean serum concentrations of TC (p = 0.043), TG (p = 0.046), LDL-C (p= 0.040), TC/HDL-C ratio (p = 0.001) and LDL-C/HDL-C ratio (p = 0.003) compared with hypertensive obese non-diabetic females. Similar results were found in hypertensive obese type 2 diabetic males compared with hypertensive obese non-diabetic males. Hypertensive obese type 2 diabetic females had significantly higher serum TC, TG and TC/HDL-C ratio (p < 0.05) than hypertensive obese type 2 diabetic males. Hypertensive obese type 2 diabetic females had significantly higher mean serum concentrations of TG (p = 0.03) and TC (p = 0.01) than obese type 2 diabetic females. There was a significant association between blood glucose and LDL-C concentrations in type 2 diabetic subjects (r = 0.36; p< 0.05).

CONCLUSIONS

Obese hypertensive type 2 diabetic females are exposed more profoundly to risk factors including atherogenic dyslipidaemia compared with males.

To detect the response of different strains of rats to an hypercholesterolemic diet, 9 different strains of male rats were fed successively a control diet (C) containing 20% casein for 4 weeks, then a high-protein, cholesterol-rich diet (HC) containing 50% casein and 1.2% cholesterol for 12 weeks. When the rats were fed the control diet, the highest cholesterolemia was found in the LOU strain and the lowest in the WAG and Brown-Norway (BN) strains. The latter strain had the highest free to esterified cholesterol ratio and showed a marked band in beta position (LDL) on agarose gel electrophoresis. Administration of the HC diet induced an increase of cholesterolemia in all the strains except in Fisher (FIS) and LOU. This hypercholesterolemic diet decreased the free to esterified cholesterol ratio only in the BN and FIS strains. On agarose gel, all the strains showed a highly increased band in pre-beta position (VLDL). On polyacrylamide gel, a single, tight band in HDL position was revealed in the BN strain, while a large band or two bands were seen in the other strains. The percentages of some apoproteins in serum total lipoproteins were determined in rats fed the HC diet; the apoprotein E level was inversely correlated to the difference between the cholesterolemia of the rats given the HC and C diets (r = - 0.72; P less than 0.05). So, the BN rats had the lowest apo E level with the highest cholesterolemia increase due to the HC diet.

A method is described for sequential separation of high density, very low density, and low density lipoproteins (HDL, VLDL, and LDL, respectively) from 100 microliters of serum, using an air-driven ultracentrifuge (Airfuge, Beckman). Cesium chloride was used for density adjustment. Precision-within-series (coefficient or variation) depended on the cholesterol concentration in the lipoprotein fractions, greater than 1 mmol/l, less than 2.3%. Recovery within-series was nearly 100%. The results (mmol/l) correlate well with those from an electrophoretic-enzymatic procedure (alpha-HDL: 1.49 +/- 0.34 vs. 1.48 +/- 0.33, r = 0.949; pre-beta-VLDL: 0.58 +/- 0.42 vs. 0.59 +/- 0.45, r = 0.975; beta-LDL: 3.11 +/- 0.93 vs. 3.07 +/- 0.88, r = 0.990; n = 48). Recovery of lipoprotein cholesterol from this group was 99.2 +/- 4.2%. A combination of ultracentrifugation with high-performance thin-layer chromatography for determination of lipoprotein-lipid profiles was achieved with recoveries of 98-101%, as evaluated from a group of healthy men (n = 31) and women (n = 38). The entire procedure is, therefore, suitable for compositional studies on lipoproteins from small serum samples. In particular, capillary serum from children of all ages, even from premature neonates, is quite adequate.

A simple and rapid method for the quantitation of cholesterol in human serum lipoproteins (VLDL, LDL, HDL2, and HDL3) was developed (1). The content of cholesterol in each lipoprotein fraction was determined by means of a commercial enzymatic reaction kit after separation by high performance liquid chromatography with gel permeation columns. The quantitation of cholesterol could be performed with only 10-20 mu l of serum in less than 50 min by measuring A550 after passing the mixed eluate and enzyme solution through an on-line reactor system of a high-speed chemical derivatization liquid chromatograph. The precision, reproducibility and sensitivity of the quantitation of cholesterol with this method were acceptable, and the values of HDL-cholesterol determined by this method correlated well with those found by the heparin-manganese chloride precipitation method (r=0.958, n=93).

BACKGROUND

Atherogenic dyslipoproteinemia is one of the most important risk factor for atherosclerotic changes development. Hypothyroidism is one of the most common causes of secondary dyslipidemias which results from reduced LDL clearance and therefore raised levels of LDL and apoB. Association between small dense LDL (sdLDL) presentation and thyroid status has been examinated using polyacrylamide gel electrophoresis for lipoprotein subfractions evaluation.

METHODS

40 patients with diagnosed autoimmune hypothyroidism and 30 patients with autoimmune hyperthyroidism were treated with thyroxine replacement or thyreo-suppressive treatment. In both groups lipid profiles, LDL subractions, apolipoproteins (apoA1, apoB), apoA1/apoB ratio and atherogenic index of plazma (AIP) were examined before treatment and in state of euthyreosis.

RESULTS

Thyroxine replacement therapy significantly reduced levels of total cholesterol (TC), LDL, triglycerides (TG) and also decreased levels of sdLDL (8,55±11,671 vs 0,83±1,693mg/dl; p<0,001), apoB and AIP. For estimation of atherogenic lipoprotein profile existence an AIP evaluation seems to be better than apoB measurement because of the more evident relationship with sdLDL (r=0,538; p<0,01). Thyreo-suppressive therapy significantly increased levels of TC, LDL, TG and apoB. The sdLDL was not found in hyperthyroid patients.

CONCLUSIONS

Atherogenic lipoprotein profile was present in 52.5% of hypothyroid subjects, which is higher prevalence than in normal, age-related population. Substitution treatment leads to an improvement of the lipid levels, TG, apoB, AIP and LDL subclasses. It significantly changed the presentation of sdLDL - we noticed shift to large, less atherogenic LDL particles. Significantly positive correlation between sdLDL and TAG; sdLDL and VLDL alerts to hypertriglyceridemia as a major cardiovascular risk factor.

Serum levels of cholesterol (C), triglycerides (TG), lipoprotein-C and apolipoproteins (apo) A-I, A-II and B were measured in 30 children with type I diabetes mellitus (16 boys, 14 girls, aged 11-14 years) and in 26 healthy controls (15 boys, 11 girls, aged 10-13 years). For 19 diabetics controls matched for age, sex and relative body weight were selected. The diabetic patients were considered to be in fair metabolic control according to HbA1 levels and glycosylated serum protein concentrations. Mean serum apo A-I, A-II and B, C, TG, low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) did not differ significantly between diabetic nondiabetic children. Very low density lipoprotein cholesterol (VLDL-C) was significantly higher in diabetic children than in controls. Serum C and LDL-C levels showed close univariate linear correlations with glycosylated serum protein (LDL-C: r = 0.53, p less than 0.01, C: r = 0.58, p less than 0.01) in diabetics. The ratio LDL/HDL-C was significantly correlated to HbA1 levels (r = 0.47, p less than 0.01). By canonical and multiple linear correlation analysis significant relations of a selected set of variables concerning the control and therapy of diabetes (serum glucose, HbA1, glycosylated serum protein, insulin dose) with a set of lipoprotein variables (C, TG, VLDL-C, HDL-C, LDL-C, apo A-I, A-II, B) could be demonstrated. From these data we conclude that significant relations between atherogenic serum lipids and lipoproteins (C, LDL-C) and the degree of metabolic control exist in diabetic children, even in the absence of marked dyslipoproteinemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Very-low-density lipoproteins (VLDLs) are the major carriers of fasting plasma triglyceride (TG). TG-enriched VLDLs become cholesterol (C)-enriched low-density lipoproteins (LDLs) through hydrolysis facilitated by lipoprotein lipase (LPL). Omega-3 fatty acid (n-3 FA) supplementation may increase LDL-C while decreasing plasma TG in hypertriglyceridemic patients. It has been proposed that n-3 FAs increase LDL-C by promoting production of TG-poor VLDL and accelerating conversion of VLDL to LDL. To study the effects of n-3 FA supplementation on in vivo lipolysis of VLDL directly, we treated 11 hypertriglyceridemic subjects with n-3 FA (3.3 g/d). Each participant was studied three times: at baseline, after a 1-month period of run-in olive oil placebo, and after 1 more month of n-3 FA supplementation. Lipolysis was induced by intravenous infusion of heparin for 2 hours. Plasma samples were obtained every 30 minutes for determination of lipids and apoproteins (apos), separation of individual lipoproteins by fast protein liquid chromatography (FPLC), and measurement of LPL and hepatic TG lipase (HTGL) levels. n-3 FA supplementation decreased fasting plasma TG (2.51 +/- 0.23 v 3.97 +/- 0.46 mmol/L), VLDL-TG (1.08 +/- 0.18 v 2.35 +/- 0.35 mmol/L), and VLDL-C (0.39 +/- 0.05 v 0.72 +/- 0.13 mmol/L) while increasing LDL-C (3.59 +/- 0.21 v 3.00 +/- 0.23 mmol/L) and plasma apo B (3.31 +/- 0.19 v 2.90 +/- 0.17 mmol/L). The absolute rate of TG lipolysis correlated with fasting TG (r = .74, P < .005) and was lower after n-3 FA supplementation (0.11 +/- 0.01 mmol/mL/min) as compared with placebo (0.19 +/- 0.01, P < .01), whereas percent decreases from baseline TG levels were similar at entry onto the study (57.4% +/- 2.5%), after placebo (58.8% +/- 2.7%), and after n-3 FA (52% +/- 3.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND

Despite the importance of oxidized LDL and small LDL particles as atherogenic lipoproteins, the relationship between oxidized LDL and the distributions of size subclasses of lipoproteins is not fully proved. We investigated the relationship of circulating malondialdehyde-modified (MDA)-LDL, an oxidized form of LDL, and lipoprotein subclasses in healthy men.

METHODS

The study group consisted of a total of 170 healthy Japanese men (55+/-9 y). Plasma cholesterol concentrations in major lipoproteins and their subclasses were determined by HPLC with gel permeation columns.

RESULTS

In univariate analysis, body mass index, waist circumference, blood pressure, white blood cell count, C-reactive protein, uric acid, fasting insulin, HOMA-IR, total cholesterol, triglycerides, each VLDL subclass cholesterol, each LDL subclass cholesterol, small HDL cholesterol, and very small HDL cholesterol were positively correlated with MDA-LDL, whereas adiponectin and large HDL cholesterol were inversely correlated with MDA-LDL. In stepwise multiple regression analysis, very small LDL cholesterol, medium VLDL cholesterol, very small HDL cholesterol, small HDL cholesterol, and systolic blood pressure were identified as independent determinants of MDA-LDL (R(2)=0.718, p<0.0001).

CONCLUSIONS

Circulating MDA-LDL concentrations are strongly associated with very small LDL cholesterol concentrations in healthy men. HDL size heterogeneity has a biphasic effect on MDA-LDL.

OBJECTIVE

To determine the effects of obesity on blood lipids and homocysteine levels of university students.

METHODS

The study comprised of 172 male and 183 female students who were classified according to their body mass index (BMI) into 3 groups as underweight, normal weight and overweight. Anthropometric measurements, blood lipids and homocysteine levels were analyzed.

RESULTS

Mean fat mass percentage (FM %), triceps, biceps, suprailiac and the sum of skinfold thickness were significantly higher in girls than boys (p < 0.001). Frequency of overweight (BMI = 25.0-30.0 kg/m2) in boys and girls was found to be 13.3% and 6.6% respectively. There was a negative correlation between the body weight and HDL-cholesterol (r = -0.33, p < 0.01), a positive correlation between WHR and VLDL-cholesterol levels (r = 0.42, p < 0.01). As long as body weight, WHR and FM (%) increase, homocysteine level also increases. Overweight students had significantly higher level of VLDL-C, triglycerides (TG), TC/HDL-C ratio and LDL-C/HDL-C ratio than normal and underweight students (p < 0.05).

CONCLUSIONS

Obesity effects blood lipid and homocysteine levels negatively. The early detection and control of obesity and the management of dyslipidemia and homocysteine levels may help reduce the risk of cardiovascular diseases in the young population.

We quantified the plasma levels and peritoneal loss of lipids and lipoproteins, and studied the composition of plasma and effluent lipoproteins in 16 patients on CAPD (5 females and 11 males, 18 to 76 years old). Five patients were studied prospectively (at 0, 1, 3 and 6 months) and 11 patients at 6 to 58 months on CAPD (N = 30). Elevated levels of plasma VLDL and reduced levels of plasma HDL were maintained in these patients throughout 58 months of CAPD, whereas the initially increased LDL levels showed a tendency towards normalization. All plasma lipoproteins (VLDL, IDL, LDL and HDL) were present in the peritoneal effluent. The lipoproteins isolated from plasma and peritoneal fluid shared a similar lipid and apolipoprotein composition. The peritoneal transport characteristics of plasma lipoproteins were similar to other plasma macromolecules. Their clearance correlated with their molecular mass, plasma concentration and dwell time, but was not affected by duration of CAPD treatment. The plasma lipid and lipoprotein levels were unaffected by the rate of glucose absorption. The peritoneal protein clearance correlated positively with plasma levels of triglyceride and LDL, and negatively with plasma HDL. An inverse correlation was observed also between plasma levels of HDL and its peritoneal clearance (r = -0.393, P less than 0.025, N = 30). The continuous peritoneal loss of HDL and the hypertriglyceridemia were found to contribute most to the persistent low plasma levels of HDL in CAPD patients, and thus may lead to the accelerated atherosclerosis observed in these patients.

OBJECTIVE

Excess visceral fat accumulation is associated with the metabolic disturbances of obesity. Differential lipid redistribution through lipoproteins may affect body fat distribution. This is the first study to investigate VLDL-triglyceride (VLDL-TG) storage in visceral fat.

METHODS

Nine upper-body obese (UBO; waist circumference >88 cm) and six lean (waist circumference <80 cm) women scheduled for elective tubal ligation surgery were studied. VLDL-TG storage in visceral, upper-body subcutaneous (UBSQ), and lower-body subcutaneous (LBSQ) fat were measured with [9,10-(3)H]-triolein-labeled VLDL.

RESULTS

VLDL-TG storage in visceral fat accounted for only ~0.8% of VLDL-TG turnover in UBO and lean women, respectively. A significantly larger proportion of VLDL-TG turnover was stored in UBSQ (~5%) and LBSQ (~4%) fat. The VLDL-TG fractional storage was similar in UBO and lean women for all regional depots. VLDL-TG fractional storage and VLDL-TG concentration were correlated in UBO women in UBSQ fat (r = 0.68, P = 0.04), whereas an inverse association was observed for lean women in visceral (r = -0.89, P = 0.02) and LBSQ (r = -0.87, P = 0.02) fat.

CONCLUSIONS

VLDL-TG storage efficiency is similar in all regional fat depots, and trafficking of VLDL-TG into different adipose tissue depots is similar in UBO and lean women. Postabsorptive VLDL-TG storage is unlikely to be of major importance in the development of preferential upper-body fat distribution in obese women.