Cyclosporin A (CsA) pharmacokinetics was studied in 19 diabetic children (mean age: 10.6 y). They were divided into prepubertal (I) and pubertal (II) groups according to plasma oestradiol or testosterone concentrations. The kinetic study was performed after a 72 h wash out period and a single oral dose of 7.5 mg/kg CsA. CsA in blood was measured by HPLC. The kinetic parameters: Cmax, tmax, t 1/2, AUC, CL/f, Vz/f and tss were calculated. No significant difference was found between the two groups. A significant negative correlation was found between Vz and both total cholesterol (r = -0.46), VLDL + LDL - cholesterol (r = -0.49) and VLDL + LDL - phospholipids (r = -0.58). CsA kinetics at steady-state were simulated by superimposition of single dose kinetics derived from each single dose. Measured steady-state blood concentrations were correlated (r = 0.80) with the values predicted by the simulation. The results suggest that CsA adjustment dosage of the CsA may be performed after a single oral dose using blood levels measured by HPLC. This procedure requires validation in further studies.

An inverse relationship has been reported between cancer risk and cholesterol level, prompting the hypothesis that hypercholesterolemia may be protective against cancer. We tested this hypothesis by evaluating the growth of Lewis lung carcinoma in three different murine models of hypercholesterolemia: Pluronic treated mice, apolipoprotein E (ApoE) deficient mice, and low density lipoprotein receptor (LDL-R) deficient mice. Only the accumulation of LDL-cholesterol in LDL-R deficient mice suppressed tumor growth. Accumulation of chylomicrons, very low density lipoproteins (VLDL), and cholesterol-enriched remnants in the Pluronic treated mice and ApoE deficient mice did not inhibit tumor growth, even though mice in all three models were equally hypercholesterolemic. Taken together, the experimental evidence from our studies indicate that high plasma cholesterol in the form of LDL-cholesterol could have a beneficial effect against cancer in vivo.

Background: Remnant cholesterol (RC) can partly explain the residual risk in atherosclerotic cardiovascular disease (ASCVD). A consensus method of measuring RC levels has not been established yet. In clinical practice, RC levels are usually calculated from the standard lipid profile, which are not true RC. Nuclear magnetic resonance (NMR) can measure RC levels directly. This study aimed to characterize RC at fasting and non-fasting states in more details and establish the performance of calculated RC and NMR-measured RC.

Methods: Blood samples at fasting state and at 2 h and 4 h postprandial states were collected in 98 subjects. Lipid parameters including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), subfractions 3, 4, and 5 of very low-density lipoprotein cholesterol (VLDL₃-C, VLDL₄-C, and VLDL₅-C, respectively), and intermediate-density lipoprotein cholesterol (IDL-C) were measured by enzymatic method and NMR. RC levels calculated from the standard lipid profile or measured by NMR were referred here as RCe or RCn.

Results: The RCe and RCn levels were different, but both of them increased after a meal (P < 0.05), especially at 4 h postprandial state. Low correlations were found between RCe and RCn in the 1st, 2nd, and 3rd quartiles of TG, but RCn showed great correlation with RCe in the highest quartile regardless of the fasting or non-fasting state (R = 0.611, 0.536, and 0.535 for 0 h, 2 h, and 4 h, respectively). However, across the 2nd and 3rd quartiles, RCe levels were nearly close to RCn levels. RCe levels tended to overestimate RCn levels in the 1st quartile of TGe levels with median differences of 0.23(- 0.13, 0.63) and underestimate RCn levels with median differences of - 0.23(- 0.33, 0.07) in the highest quartile of TGe levels.

Conclusions: RC calculated from the standard lipid profile as TC minus LDL-C minus HDL-C is different from the NMR-measured RC. According to different TG levels, RC could overestimate or underestimate the actual RC level. Developing a consensus clinical method to measure RC levels is necessary, so that results from different studies and platforms can be more directly compared.

Trial registration: Chinese Clinical Trial Registry, ChiCTR1900020873. Registered in 21 January 2019 - Retrospectively registered.

Keywords: Atherosclerotic cardiovascular disease; Enzymatic method; Fasting state; Nuclear magnetic resonance; Postprandial state; Remnant cholesterol; Remnant lipoproteins; Residual risk.

A non-competitive enzyme linked immunosorbent assay (ELISA) has been developed to quantitate apolipoprotein E (Apo E) concentrations in serum and in isolated lipoproteins. Microtiter plates coated with affinity-purified antibodies to Apo E were used and the Apo E bound to the plates was estimated with peroxidase-labelled antibodies to Apo E. The average concentration of Apo E in the serum from normolipidemic subjects (n = 132) was 54 +/- 19 mg/l. The within and between assay coefficients of variation were 4.65 and 7.08%, respectively. The standard curves for Apo E in serum, in VLDL and in HDL were parallel. There was a good correlation (r = 0.81) between estimation of Apo E by our assay and that by electroimmunoassay. Assay sensitivity (1 ng of Apo E) was sufficient to enable a study of the distribution of Apo E in plasma lipoproteins separated by density gradient ultracentrifugal fractionation.

BACKGROUND

Alterations in lipoprotein size are associated with increased cardiovascular disease risk. Higher hemoglobin levels may indicate a higher risk of atherosclerosis and was previously associated with obesity, metabolic syndrome, and insulin resistance. No previous studies have investigated an association between hemoglobin concentration and lipoprotein particle size.

METHODS

We conducted a population-based, cross-sectional study of 766 Caucasian, middle-aged subjects (341 men and 425 women) born in Pieksämäki, Finland, who were categorized into five age groups. The concentrations and sizes of lipoprotein subclass particles were analyzed by high-throughput nuclear magnetic resonance (NMR) spectroscopy.

RESULTS

Larger very low density lipoprotein (VLDL) particle diameter was associated with higher hemoglobin concentrations in men (p = 0.003). There was a strong relationship between smaller high density lipoprotein (HDL) particle size and higher hemoglobin concentration in both men and women as well as with smaller low density lipoprotein (LDL) particle size and higher hemoglobin concentration in men and women (p < 0.001; p = 0.009, p = 0.008). VLDL particle concentration had a moderate positive correlation with hemoglobin concentration (r = 0.15; p < 0.001). LDL particle concentration showed a statistical trend suggesting increasing particle concentration with increasing hemoglobin levels (r = 0.08; p = 0.05).

CONCLUSIONS

Higher hemoglobin levels are associated with larger VLDL, smaller LDL, and smaller HDL particle sizes and increasing amounts of larger VLDL and smaller LDL particles. This suggests that a higher hemoglobin concentration is associated with an unfavorable lipoprotein particle profile that is part of states that increase cardiovascular disease risk like diabetes and metabolic syndrome.

The major lipid disturbance in children with congenital nephrosis of the Finnish type (CNF) is hypertriglyceridaemia. To determine whether or not hypertriglyceridaemia is caused by defective triglyceride catabolism, we measured lipoprotein lipase (LPL) activities and masses at various stages of the disease. At age 3 months in CNF both LPL activity and mass were decreased, but a close positive correlation between these parameters similar to that in controls was observed. At age 9 months both LPL activity and mass were even lower. At that time a significant positive correlation (r = 0.72, P < 0.05) between LPL activities and albumin concentrations and significant negative correlations between plasma free fatty acid (FFA) concentrations and LPL activities (r = -0.72, P < 0.05) and between plasma FFA concentrations and serum albumin concentrations (r = -0.73, P < 0.05) were observed, suggesting that low albumin concentrations result in increase of FFA levels, which could interfere with a normal LPL function at the endothelial surface. On dialysis after nephrectomy, LPL activities and masses increased. At age 3 and 9 months apoprotein C-II (apo C-II) and apoprotein C-III (apo C-III) levels were not decreased although apoproteins were being lost into the urine. On dialysis the mean ratio of apo C-II/C-III was significantly lower than the mean in controls (P < 0.001). We conclude that impaired function of LPL seems to be the major cause of hypertriglyceridaemia and disintegrity of the VLDL-IDL-LDL delipidation cascade in children with CNF.

OBJECTIVE

To examine the relationship between lipid values and BMI (body mass index) on hospitalizations in hemodialysis (HD) patients.

METHODS

Retrospective (2-year) study.

METHODS

Outpatient dialysis center in a large metropolitan city.

METHODS

This study used 158 HD patients stratified on the basis of ethnicity (non-Black and Black) and diabetic status (nondiabetic and diabetic).

METHODS

Subjects were observed for 2 years. Body weight, BMI, lipid parameters, and hospitalization duration were determined 8 times (3-month intervals).

METHODS

Body weight, BMI, lipid parameters (serum triglyceride concentration, serum total cholesterol, high-density lipoprotein [HDL]-, low-density lipoprotein [LDL]-, very low-density lipoprotein [VLDL]- cholesterol concentrations, serum Apo-protein A1 [Apo-A1] concentration, and serum Apo-protein B [Apo-B] concentration), and morbidity data were recorded.

RESULTS

Hemodialysis subjects were hospitalized 2.3 +/- 1.6 times over the 2-year experimental period. Length of hospital stay averaged 6.6 +/- 0.5 days/hospitalization. Length of hospital stay was inversely related to HDL concentration (r = -0.21, P <.05, n = 89), but not significantly related to BMI in HD subjects. BMI was positively associated with LDL concentration (r = +0.28, P <.01, n = 97). Cholesterol concentration was directly associated with LDL concentration (r = +0.52, P <.01, n = 138), VLDL concentration (r = +0.47, P <.01, n = 139), and triglyceride concentration (r = +0.54, P <.01, n = 155). Mean concentration of HDL-cholesterol was inversely related serum triglyceride concentration (r = -0.43, P <.01, n = 140). Although Apo-A1 concentration was directly associated with HDL level (r = +0.39, P <.01, n = 139), Apo-B was inversely related to HDL level (r = -0.37, P <.01, n = 138) and directly related to cholesterol concentration (r = +0.71, P <.01, n = 138), VLDL concentration (r = +0.87, P <.01, n = 138), and triglyceride concentration (r = +0.81, P <.01, n = 138).

CONCLUSIONS

Cardiac disease remains the primary cause of morbidity and mortality in HD patients, and results of the present study suggest that dyslipidemias present in the HD population negatively impact cardiovascular profiles which, in turn, influence the frequency/duration of hospitalizations. Among all lipid parameters analyzed in the present study, increased LDL and decreased HDL concentrations were more strongly related to length of hospital stay than was BMI.

In order to evaluate the toxicity of hypervitaminosis A in regular dialysis patients, the relationships between the plasma levels of vitamin A, retinol binding protein (RBP), prealbumin (PA), and biochemical parameters were studied in 47 patients. Plasma vitamin A levels were inversely correlated with hematocrit (r = -0.5), which was also significantly correlated with RBP/vitamin A ratio (r = 0.61). Immunoreactive parathyroid hormone (i-PTH) and very low density lipoprotein (VLDL) were inversely related to RBP/vitamin A and RBP/PA ratios. These findings suggest that a raised plasma vitamin A level in regular dialysis patients contributes to anemia and hypervitaminosis A toxicity.

The relationship of diet and physical activity with metabolic syndrome (MS) was studied among 60 male and female (40-60 y) urban Indian MS patients. Intake of green leafy vegetables, other vegetables, fruits and milk were significantly (p ≤ .01) associated with reduced fat mass and waist circumference and increased lean body mass. Energy, carbohydrates, and fat intakes were significantly (p ≤ .01) correlated with increased body fat and waist circumference and reduced lean body mass. Energy, total and saturated fat intake were positively and significantly (p ≤ .05; .01) correlated with total cholesterol. Total fat was also significantly (p ≤ .05; .01) correlated with increased systolic blood pressure (r = 0.33), serum triglycerides (r = 0.33), LDL-C (r = 0.29) and VLDL-C (r = 0.28). Increased TDEE was significantly (p ≤ .01) associated with decreased body fat and waist circumference (r = 0.53 and 0.60) and increased lean body mass (r = 0.68).

Proton nuclear magnetic resonance spectra at 500 MHz of plasma and the very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) fractions isolated by KBr gradient ultracentrifugation were analysed in 16 cancer patients, six pregnant and nine non-pregnant healthy subjects. In spectra with narrow plasma composite aliphatic peaks (methylene at 1.2-1.4 p.p.m. and methyl at 0.8-0.9 p.p.m., respectively), a relative increase in either VLDL, LDL, or both, or a decrease in HDL signals was observed. The mechanism for line-width narrowing seemed different in cancer patients (less signals from HDL relative to VLDL) compared with pregnant women (more signals from LDL). By reconstitution of plasma samples from both healthy subjects and patients with malignant disease, decreased concentration of VLDL or HDL resulted in broadening or narrowing of the composite peaks, respectively. The effects of VLDL and HDL on the plasma line width were moderated by the signals from LDL. Within lipoprotein fractions, the methylene and methyl resonances were shifted to a higher field with increased observation temperature, the change in shift being greatest for HDL. The line width of composite peaks in plasma varied with the observation temperature, depending on the relative concentrations of individual lipoproteins. The correlation coefficient (r) for the relation between total plasma triglyceride level and the average of the line-width of the composite methylene and methyl peaks was -0.78 (p less than 0.001). For spectra of individual lipoproteins, statistical significant relationships were found between line-widths and triglyceride content of the LDL fraction (methyl line-width, r = -0.63) (p less than 0.001) and between methylene line-width and cholesterol of HDL (r = 0.54) (p = 0.003). In summary, the shape and width of the composite aliphatic peaks of plasma were affected by the relative concentration, chemical shift and transition temperature of both VLDL, LDL, and HDL, and by the total triglyceride level. Comparing pregnancy and malignant disease, the lipoprotein resonances contributed differently in giving narrow composite signals.

After reviewing the general characteristics of lipids (LDL-C, VLDL-C, HDL-C) and atherothrombosis, including the I-VIII degrees of its histopathological arterial lesions (with contributions of J. E. Edwards and R. Virmani), the authors described the P. Libby's data on lipoprotein-associated phospholipaseA2 (Lp-PLA2) and its two inflammatory mediators: lysophosphatidylcholine and oxidized nonesterified fatty acids. They are involved in plaque progression and vulnerability. Lp-PLA2 is an emerging proinflammatory marker. The new drug darapladib inhibits Lp-PLA2 and acts against inflammation. LDL-C is present in the atherosclerotic plaque from the circulating blood in arterial lumen (through the dysfunctional endothelium) and vasa vasorum as well as after the decomposition of foam cells (monocytes-phagocytes, smooth muscle and dendritic cells) and outpoured erythrocytes (its membranes) after hemorrhage. The blood from the arterial lumen can also enter the atherosclerotic plaque through the lesions in its fibrous cap (erosion, fissure, rupture). Atherosclerosis as a disease or as an inevitable accompaniment of aging ("the senescence hypothesis"). The familial hypercholesterolemia is usually due to mutation of just one gene--a defective LDL-C receptor gene on chromosome 19. The accelerated and severe atherosclerosis very resistant to therapy occurs. The patients with homozygous familial hypercholesterolemia can die of myocardial infarction in early childhood. Therapeutic decrease of LDL-C and increase of HDL-C slows down the evolution of atherosclerosis, stabilizes the atherosclerotic plaques, and even brings about their partial regression. Statins, niacin, ezetimibe, LDL-C apheresis, and surgery: shunt between the portal and inferior caval veins, liver transplantation, and partial ileal bypass. The elevated LDL-C is the most established risk factor for atherosclerosis with impact on coronary heart disease mortality of 26%, and it should be the primary target of preventive and therapeutic efforts.

During the periparturient transition period, negative energy balance (NEB) characterized by high concentrations of non-esterified fatty acids (NEFA) may cause fatty liver and ketosis in dairy cows. Previous studies have shown that the protein kinase R-like endoplasmic reticulum kinase (PERK) branch of the endoplasmic reticulum stress (ERS) response plays an important role in lipid metabolism in hepatocytes. This study, therefore, investigated the role of the PERK-branch in NEFA-induced fatty liver. Different concentrations of NEFA or GSK2656157 (a novel catalytic inhibitor of PERK) were used to treat hepatocytes isolated from calves. The NEFA treatment significantly increased the triacylglycerol (TG) content, the phosphorylation level of PERK and eukaryotic initiation factor 2α (eIF2α), and the abundance of glucose-regulated protein 78 (Grp78), C/EBP homologous protein (CHOP), sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FASN), peroxisome proliferator-activated receptor-α (PPARα), carnitine palmitoyltransferase 1A (CPT1A), apolipoprotein B (APOB), and the low-density lipoprotein receptor (LDLR). Compared with the 1.2 mM NEFA group, inhibition of PERK activity further increased the TG content in hepatocytes, the very-low-density lipoprotein (VLDL) content in the supernatant and the protein abundance of APOB while reducing the expression and nuclear levels of SREBP-1c and PPARα, as well as the expression of CPT1A and CPT2. In conclusion, the results showed that the NEFA-induced PERK-eIF2α signaling pathway promotes lipid synthesis, lipid oxidation, but inhibits the assembly and secretion of VLDL. Therefore, during the transition period, the activation of the PERK-eIF2α signaling pathway in the liver of dairy cows could defeat the acid-induced lipotoxicity and provide energy to alleviate NEB.

Keywords: Dairy cows; Lipid metabolism; Non-esterified fatty acids; Protein kinase R-like endoplasmic reticulum kinase.

<st<em>r</em>ong class="sub-title"> Objectives: </st<em>r</em>ong> The cu<em>r</em><em>r</em>ent study examines the placental and mate<em>r</em>nal lipid p<em>r</em>ofile and exp<em>r</em>ession of genes involved in placental lipid metabolism in women with p<em>r</em>eeclampsia.

<st<em>r</em>ong class="sub-title"> Methods: </st<em>r</em>ong> The cu<em>r</em><em>r</em>ent study includes no<em>r</em>motensive cont<em>r</em>ol women (n = 40) and women with p<em>r</em>eeclampsia (n = 39). P<em>r</em>eeclampsia women we<em>r</em>e fu<em>r</em>the<em>r</em> classified into women delive<em>r</em>ing at te<em>r</em>m p<em>r</em>eeclampsia (T-PE; n = 15) and p<em>r</em>ete<em>r</em>m p<em>r</em>eeclampsia (PT-PE; n = 24).

<st<em>r</em>ong class="sub-title"> Results: </st<em>r</em>ong> The<em>r</em>e we<em>r</em>e no significant diffe<em>r</em>ences in mate<em>r</em>nal lipid p<em>r</em>ofile between the T-PE and no<em>r</em>motensive cont<em>r</em>ol g<em>r</em>oups. Mate<em>r</em>nal plasma <em>VLDL</em> (P < 0.05) and <em>r</em>atios of total choleste<em>r</em>ol : HDL (P < 0.05), athe<em>r</em>ogenic index [log (t<em>r</em>iglyce<em>r</em>ides/HDL)] (P < 0.01) and apolipop<em>r</em>otein B : apolipop<em>r</em>otein A (P < 0.05) we<em>r</em>e highe<em>r</em> in the PT-PE g<em>r</em>oup as compa<em>r</em>ed with the no<em>r</em>motensive cont<em>r</em>ol g<em>r</em>oup. Placental total choleste<em>r</em>ol and HDL levels we<em>r</em>e highe<em>r</em> (P < 0.05) in the T-PE as compa<em>r</em>ed with the no<em>r</em>motensive cont<em>r</em>ol g<em>r</em>oup. Highe<em>r</em> placental t<em>r</em>iglyce<em>r</em>ides (P < 0.05) we<em>r</em>e obse<em>r</em>ved in PT-PE g<em>r</em>oup compa<em>r</em>ed with T-PE g<em>r</em>oup. Placental mRNA levels of pe<em>r</em>oxisome p<em>r</em>olife<em>r</em>ato<em>r</em> activated <em>r</em>ecepto<em>r</em> α, ca<em>r</em>nitine palmitoyl t<em>r</em>ansfe<em>r</em>ase-1, cluste<em>r</em> of diffe<em>r</em>entiation 36 and lipop<em>r</em>otein lipases we<em>r</em>e lowe<em>r</em> (P < 0.05) in the PT-PE than no<em>r</em>motensive cont<em>r</em>ol g<em>r</em>oup. A negative association of mRNA levels of pe<em>r</em>oxisome p<em>r</em>olife<em>r</em>ato<em>r</em> activated <em>r</em>ecepto<em>r</em> α (<em>r</em> = -0.246, P = 0.032; <em>r</em> = -0.308, P = 0.007, <em>r</em>espectively), ca<em>r</em>nitine palmitoyl t<em>r</em>ansfe<em>r</em>ase-1 (<em>r</em> = -0.292, P = 0.011; <em>r</em> = -0.366, P = 0.001), lipop<em>r</em>otein lipases (<em>r</em> = -0.296, P = 0.010; <em>r</em> = -0.254, P = 0.028) with SBP and DBP was obse<em>r</em>ved. The<em>r</em>e was a positive association of placental t<em>r</em>iglyce<em>r</em>ides (<em>r</em> = 0.244, P = 0.031) with DBP.

<st<em>r</em>ong class="sub-title"> Conclusion: </st<em>r</em>ong> Women with p<em>r</em>eeclampsia exhibit highe<em>r</em> lipid : lipop<em>r</em>otein <em>r</em>atios suggesting an athe<em>r</em>ogenic state pa<em>r</em>ticula<em>r</em>ly in women delive<em>r</em>ing p<em>r</em>ete<em>r</em>m. Lowe<em>r</em> exp<em>r</em>ession of genes involved in placental fatty acid oxidation and t<em>r</em>anspo<em>r</em>t was also obse<em>r</em>ved in p<em>r</em>eeclampsia.

The effects of different dietary fats with variable levels of polyunsaturated fatty acids (PUFAs) on egg quality of Shan Partridge Duck, serum, and yolk lipid parameters were examined in this study. A flock of 585 optimal produced ducks were selected and diets enriched with 0.5%, 1%, or 2% fish oil (F)/flaxseed oil (FL)/rapeseed oil (R)/tallow (T) plus basal diet were supplied through a 28-d period. Supplemental fat source and fat level had no effects on egg qualities. Proportions of yolk total cholesterol (TC), saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) were reduced (P < 0.001), while polyunsaturated fatty acids (PUFAs), ω-6 polyunsaturated fatty acids (n-6 PUFAs), ω-3 polyunsaturated fatty acids (n-3 PUFAs), Docosahexaenoic Acid (DHA), and Eicosapentaenoic Acid (EPA) were increased by fish oil, flaxseed oil, or rapeseed oil. Effects of supplementation increasing DHA and EPA were detected in F, FL, and R. Compared with C, fish oil significantly increased low-density lipoprotein cholesterol (LDL-C) in serum, flaxseed oil significantly reduced TC and increased very low-density lipoprotein cholesterol (VLDL-C), rapeseed oil significantly reduced TC and LDL-C in serum and increased VLDL-C, tallow significantly increased LDL-C. It is concluded that unsaturated fatty acids rich diets (fish oil, flaxseed oil, and rapeseed oil) might increase yolk PUFAs, reduce yolk cholesterol, and change serum lipid parameters without evident effect on egg qualities.

Plasma very-low density lipoprotein (VLDL) and vitellogenin (VTG) from mature female Japanese quail (Coturnix coturnix japonica) and chickens (Gallus domesticus) were isolated and digested in vitro with cathepsin D (EC3.4.23.5). The incubation mixtures were then reduced and subjected to gradient (4.5-18%) SDS-polyacrylamide gel electrophoresis. Protein fragments were stained with either Coomassie Brilliant Blue R-250 (VLDL digests) or Coomassie Brilliant Blue R-250 containing 20 mM AlCl3 (VTG digests). Fragments resulting from the in vitro enzymatic digestion of quail and chicken plasma VLDL-apolipoprotein B (apo B) and VTG closely resembled those produced in vivo and isolated from egg yolks of each respective species. Phosvitin, a proteolytically derived fragment of VTG, primarily existed as a single band (M(r) approximately 42 kDa) in Japanese quail yolk granules. In contrast, chicken phosvitin mainly consisted of a cluster of phosphoproteins ranging in size from approximately 37 to 45 kDa. In addition to reporting a novel species difference in phosvitin moieties, the present study is the first to examine the role of cathepsin D in the generation of egg yolk proteins from plasma precursors in Japanese quail. Confirmatory evidence also was provided concerning the important role of this aspartic endopeptidase in the proteolytic cleavage of plasma VLDL-apo B and VTG in the chicken.

This short report describes the relationships between concentrations of ceramides (CER), diacylglycerols (DAG), triacylglycerols (TAG) in very low-density lipoproteins (VLDL) particles, and hepatic lipid accumulation. VLDL particles were isolated from male subjects (n = 12, mean ± SD, age 42.1 ± 5.4 years, BMI 37.4 ± 4.1 kg/m² , ALT 45 ± 21 U/L) and apolipoprotein B100 (apoB100), VLDL-TAG, -CER, and -DAG quantified. The contents of all three lipids were highly correlated with VLDL particle number (r ≥ 0.768, p ≤ 0.003). The molar quantity of VLDL-TAG was 3× that of DAG and 137× that of CER (14,053 ± 5714, 5004 ± 2714, and 105 ± 49 mol/mol apoB100, respectively). Reduced VLDL-CER concentrations were associated with both higher insulin levels (r = -0.645, p = 0.024) and intrahepatic-TAG (r = -0.670, p = 0.017). In fatty liver, the secretion of hepatic TAG, CER, and DAG may be suppressed and contribute to intrahepatic lipotoxicity. The mechanisms by which hepatic-CER and -DAG synthesis and assembly into VLDL is coordinately controlled with TAG will be important in understanding the emerging role of elevated CER contributing to cardiometabolic disease.

This study aims to establish relationships between inflammatory status, ferrokinetics and lipid metabolism in patients with diabetes mellitus. Subclinical inflammation was assessed by levels of high-sensitive C-reactive protein, tumor necrosis factor-α and erythrocyte sedimentation rate. Iron metabolism parameters included complete blood count, serum iron, transferrin and ferritin. Metabolic status assessment included lipid profile, glycated hemoglobin and microalbuminuria measurement. As a result of the study it was possible to establish both general (universal) and diabetes mellitus (DM) type-dependent relationships between the parameters of lipid profile and metabolic control in DM. High-density lipoprotein cholesterol (HDL-C) levels negatively correlated with microalbuminuria (r = -0.293; p ˂ 0.05 for type 1 diabetes and r = -0.272; p ˂ 0.05 for type 2 diabetes). Ferritin concentration positively correlated with triglyceride level (r = 0.346; p ˂ 0.05 for type 1 diabetes and r = 0.244; p ˂ 0.05 for type 2 diabetes). In type 1 diabetes, a negative correlation was discovered between estimated glomerular filtration rate (eGFR) and LDL-C (r = -0.480; p ˂ 0.05), very low-density-lipoprotein cholesterol (VLDL-C) (r = -0.490; p ˂ 0.05) and triglycerides (r = -0.553; p ˂ 0.05), and a positive one between C-reactive protein concentration and triglyceride level (r = 0.567; p ˂ 0.05). Discovered relationships between lipid profile indices, inflammatory status and microalbuminuria confirmed mutual influence of hyperlipidemia, inflammation and nephropathy in diabetes patients. Obtained results justify the strategy of early hypolipidemic therapy in patients with diabetes mellitus to prevent the development and progression of microvascular complications.

<st<em>r</em>ong class="sub-title"> Keywo<em>r</em>ds: </st<em>r</em>ong> C-<em>r</em>eactive p<em>r</em>otein; anemia of ch<em>r</em>onic disease; diabetes mellitus; e<em>r</em>yth<em>r</em>ocyte sedimentation <em>r</em>ate; hype<em>r</em>lipidemia; inflammation; i<em>r</em>on deficiency anemia; tumo<em>r</em> nec<em>r</em>osis facto<em>r</em>-α.

Diabetes mellitus is one of the most common endocrine disorders in the world. This systematic review was conducted with focus on the current knowledge on the effect of royal jelly on metabolic variables in diabetes mellitus. PubMed, Scopus, Embase, ProQuest and Google Scholar databases were searched from inception until June 2018. All clinical trials and animal studies that evaluated the effects of royal jelly on diabetes mellitus, and were published in English-language journals were eligible. Studies that provided insufficient outcomes were excluded. Out of 522 articles found in the search, only twelve articles were eligible for analysis. Seven studies showed a significant reduction in FBS, and one reported HbA1c decrease following royal jelly supplementation. Although royal jelly supplementation resulted in significant reductions in HOM A-I R in three studies, the findings on insulin levels were controversial. In addition, royal jelly substantially improved serum levels of triglycerides, cholesterol, HDL, LDL, VLDL and Apo-A1 in diabetes mellitus. In addition, royal jelly resulted in a decrease oxidative stress indicators and increase antioxidant enzymes levels. In conclusion, royal jelly could improve glycemic status, lipid profiles and oxidative stress in diabetes mellitus. However, exploring the underlying mechanisms warrants further studies.

Laying female quail of five strains (R-1, randombred control; HP and LP, high or low concentration of egg yolk very low density lipoprotein (VLDL) precursor in laying females: HW and LW, high or low 4-week body weight) were sampled after 120 days of egg production for body weight, liver weight, ovarian follicle production, and carcass composition. Body weight change during the reproductive period was associated with starting body weight, but not with yolk VLDL precursor (total plasma phosphorus). Egg production was slightly depressed in both the HW and HP strains. Liver weight was associated with body weight. Percent dry matter of liver was not different between strains. Liver as a percentage of body weight was slightly greater in the HP strain. Egg and yolk weights were associated with body weight but not with concentration of yolk VLDL precursor. Ovarian follicle number and weight were also influenced by body weight but not by concentration of yolk VLDL precursor. Carcass composition was influenced by body weight. The larger HW strain contained more fat and less protein than the smaller LW strain after 120 days of egg production.

OBJECTIVE

It has been reported that LDL inhibits endothelium-dependent relaxation (EDR) and that HDL can neutralize this effect. However, the atherogenic properties of VLDL have been so far difficult to demonstrate. Studies on VLDL are controversial, and nothing is known about the role of HDL on potential VLDL vascular actions. We examined the effect of human VLDLs on EDR, and the role of HDL in this system.

METHODS

VLDL (n=14) and LDL (n=6) were isolated from volunteer subjects. Normal HDL was obtained from one healthy donor. VLDL ability to inhibit ACh-induced vasorelaxation (10(-9)-10(-5)mM) on aortic rings previously precontracted by noradrenaline (10(-8)mM) was measured in the presence and absence of HDL.

RESULTS

ACh-induced maximal relaxation (R%) was mildly, but not significantly attenuated in the presence of VLDL (72±7%), while LDL caused a significant inhibition (60±10%, p<0.05) when compared to incubation in the absence of lipoproteins. VLDLs were subdivided into 2 groups depending on their cholesterol/triglyceride ratio: 0.18-0.22 (n=8) was considered typical and 0.10-0.15, rich in triglycerides (VLDLRT, n=6). Typical VLDL had no effect on EDR (p=0.38), however R% from VLDLRT was lower (54±7%, p<0.01) similar to the one obtained with LDL (p=0.32). HDL showed favorable effects on EDR inhibition induced by the presence of VLDLRT (p<0.05.).

CONCLUSIONS

Although typical VLDL did not cause endothelial dysfunction, triglyceride-enriched VLDL had inhibitory effect on EDR. It is proposed that alterations in VLDL composition would increase its atherogenic capacity. Moreover HDL appears to protect endothelium from VLDL action.

OBJECTIVE

To determine body composition, coronary risk factors and physical activity and the inter-relationships of these variables in Singaporean school children.

METHODS

This study examined 1681 children (784 boys and 897 girls) from eight primary and seven secondary schools to determine percentiles for body stature and composition, blood pressure, lipids/lipoproteins and blood glucose by gender for three age divisions. An exercise and leisure pursuit questionnaire was administered to ascertain self-reported physical activity patterns. Anthropometric data and blood pressure readings were taken. Capillary blood was drawn from each child via finger prick sampling following an overnight fast. The concentrations of total cholesterol (TCHOL), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and glucose (GLU) were determined from plasma using a dry chemistry analyser. Low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL) and the TCHOL/HDL-C ratio were determined by calculation.

RESULTS

While 47.7% of boys and 22.0% of girls disclosed active lifestyles, differences between the active and non-active children were found in coronary risk factors TCHOL, LDL-C, TG, TCHOL/HDL-C and per cent body fat. No differences were shown between the two groups in HDL-C, GLU and blood pressure. There was a high correlation between the various measures of body composition with the highest correlation (r = 0.806, P < 0.001) found between body mass index (BMI) and waist measurements.

CONCLUSIONS

Children in this study who reported no activity or relatively little activity were found to have TCHOL, LDL-C, TG, TCHOL/HDL-C and per cent body fat that were higher than those who reported moderately high or vigorous physical activity patterns.

OBJECTIVE

Patients with systemic lupus erythematosus (SLE) suffer from accelerated atherosclerosis. Their most common cause of death is a cardiovascular disease (CVD), in spite of the presence of moderate lipid alterations and normal cardiovascular risk scores. However, cholesterol still accumulates in the arteries of SLE patients, so we aim to identify additional factors that may help explain the residual risk that exists in these patients. We focus on investigating whether the net charge contributes significantly to both the development and the progression of atherosclerosis in patients with SLE.

METHODS

The lipoproteins from 78 patients with SLE and 32 controls were isolated via sequential ultracentrifugation. Lipoprotein subclasses distributions were analyzed via nuclear magnetic resonance spectroscopy and the net charges of very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were measured using a Zetasizer Nano-ZS. The degree of atherosclerosis (carotid intima-media thickness [cIMT]) was determined in all the participants.

RESULTS

Each lipoprotein class exhibited a negative net charge. IDL and LDL net charge correlated negatively with cIMT (r = -0.274, P = 0.034; r = -0.288; P = 0.033, respectively) in patients with SLE. This effect was independent of age, body mass index (BMI), gender, tobacco consumption, high-sensitivity C-reactive protein (hsCRP), lipid concentration and lipoprotein particle number. LDL net charge explained 4% of the cIMT variability among these patients; this contribution was also independent of age, BMI, gender, tobacco consumption, lipids levels, apolipoproteins and hsCRP.

CONCLUSIONS

Low-density lipoprotein net charge may be considered a new independent contributor to subclinical atherosclerosis in SLE patients. The observed relationship was independent of lipid concentrations and extends the prominent role that IDL and LDL play in cardiovascular risk.

<p><div><b>OBJECTIVE</b></div>To cla<em>r</em>ify the association between PCSK9 (p<em>r</em>op<em>r</em>otein conve<em>r</em>tase subtilisin/kexin type 9) and Lp(a) (Lipop<em>r</em>otein [a]), we studied Lp(a) kinetics in patients with loss-of-function and gain-of-function <i>PCSK9</i> mutations and in patients in whom extended-<em>r</em>elease niacin <em>r</em>educed Lp(a) and PCSK9 concent<em>r</em>ations. App<em>r</em>oach and Results: Six healthy cont<em>r</em>ols, 9 hete<em>r</em>ozygous patients with familial hype<em>r</em>choleste<em>r</em>olemia (5 with low-density lipop<em>r</em>otein <em>r</em>ecepto<em>r</em> [<i>LDLR</i>] mutations and 4 with <i>PCSK9</i> gain-of-function mutations) and 3 patients with hete<em>r</em>ozygous dominant-negative <i>PCSK9</i> loss-of-function mutations we<em>r</em>e included in the p<em>r</em>elimina<em>r</em>y study. Eight patients we<em>r</em>e en<em>r</em>olled in a second study assessing the effects of 2 g/day extended-<em>r</em>elease niacin. Apolipop<em>r</em>otein kinetics in <em>VLDL</em> (ve<em>r</em>y-low-density lipop<em>r</em>otein), LDL (low-density lipop<em>r</em>otein), and Lp(a) we<em>r</em>e studied using stable isotope techniques. Plasma Lp(a) concent<em>r</em>ations we<em>r</em>e inc<em>r</em>eased in <i>PCSK9</i>-gain-of-function and familial hype<em>r</em>choleste<em>r</em>olemia-<i>LDLR</i> g<em>r</em>oups compa<em>r</em>ed with cont<em>r</em>ols and <i>PCSK9</i>-loss-of-function g<em>r</em>oups (14±12 ve<em>r</em>sus 5±4 mg/dL; <i>P</i>=0.04), but no change was obse<em>r</em>ved in Lp(a) f<em>r</em>actional catabolic <em>r</em>ate. Subjects with <i>PCSK9</i>-loss-of-function mutations displayed <em>r</em>educed apoE (apolipop<em>r</em>otein E) concent<em>r</em>ations associated with a <em>VLDL</em>-apoE absolute p<em>r</em>oduction <em>r</em>ate <em>r</em>eduction. Lp(a) and <em>VLDL</em>-apoE absolute p<em>r</em>oduction <em>r</em>ates we<em>r</em>e co<em>r</em><em>r</em>elated (<i><em>r</em></i>=0.50; <i>P</i><0.05). ApoE-to-apolipop<em>r</em>otein (a) mola<em>r</em> <em>r</em>atios in Lp(a) inc<em>r</em>eased with plasma Lp(a) (<i><em>r</em></i>=0.96; <i>P</i><0.001) but not with PCSK9 levels. Extended-<em>r</em>elease niacin-induced <em>r</em>eductions in Lp(a) and <em>VLDL</em>-apoE absolute p<em>r</em>oduction <em>r</em>ate we<em>r</em>e co<em>r</em><em>r</em>elated (<i><em>r</em></i>=0.83; <i>P</i>=0.015). In cont<em>r</em>ast, PCSK9 <em>r</em>eduction (-35%; <i>P</i>=0.008) was only co<em>r</em><em>r</em>elated with that of <em>VLDL</em>-apoE absolute p<em>r</em>oduction <em>r</em>ate (<i><em>r</em></i>=0.79; <i>P</i>=0.028).</p><Abst<em>r</em>actText><em>VLDL</em>-apoE p<em>r</em>oduction could dete<em>r</em>mine Lp(a) p<em>r</em>oduction and/o<em>r</em> assembly. As PCSK9 inhibito<em>r</em>s <em>r</em>educe plasma apoE and Lp(a) concent<em>r</em>ations, apoE could be the link between PCSK9 and Lp(a).</Abst<em>r</em>actText>

Studies designed to examine effects of fat mass reduction (including lipodystrophy and lipectomy) on human serum total and LDL-cholesterol concentrations are inconsistent. The purpose of this study was to examine effect of partial lipectomy in rats (as an experimental model of fat mass reduction in humans) on (1) circulating total cholesterol, LDL-cholesterol + VLDL-cholesterol and HDL-cholesterol concentrations, and (2) factors which may affect serum cholesterol concentrations such as: (a) liver LDL-receptor level, (b) expression of liver PCSK9 and (c) circulating PCSK9 concentration. Reduction of rat adipose tissue mass resulted in an increase in circulating total and LDL + VLDL-cholesterol concentrations, which was associated with (a) decrease in liver LDL-R level, (b) increase in liver PCSK9 expression, and (c) increase in circulating PCSK9 concentration as compared with sham controls. These changes were accompanied by elevated liver HNF1α (and HNF4α) mRNA levels. Silencing HNF1α in HepG2 cells by siRNA led to decrease in PCSK9 mRNA levels. This suggests that overexpression of HNF1α gene in liver of lipectomized rats can lead to overproduction of PCSK9. In conclusion, up-regulation of PCSK9, due to overexpression of HNF1α gene in liver of lipectomized rats and subsequently increase in circulating PCSK9 concentration lead to decrease in liver LDL-R level. This may contribute, at least in part, to an increase in the concentration of circulating cholesterol in rats with reduced fat mass. These findings provide a possible explanation for the molecular mechanism of hypercholesterolemia observed sometimes after reduction of fat mass in human.