Serum concentrations of non-esterified fatty acids (NEFA) and very low-density lipoprotein (VLDL) in close-up dairy cattle were compared in relation to parity. Data were obtained from 37 nulli/primiparous (NP) and 24 multiparous (MU, parity: 2-7) cows between 14 days and 1 day prepartum. A positive correlation (r=0.684, P<0.01) was found between serum NEFA and VLDL concentrations in NP cows. Among the VLDL constituents, the NEFA concentration was particularly correlated with the triglyceride (TG) concentration (r=0.658, P<0.01). However, no significant correlation was found between the concentrations of NEFA and VLDL or VLDL-TG in MU cows (r=-0.028 and 0.307). These results suggest the presence of higher hepatic secretion of NEFA-derived VLDL in NP cows.

Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of tissue factor (TF)-induced blood coagulation. A positive association between very low density lipoproteins (VLDLs) and TFPI has been reported in vivo. In contrast, one in vitro study indicates that TFPI may enhance lipoprotein lipase (LPL) activity, thereby increasing triglyceride hydrolysis. The current study was conducted to investigate how native VLDL influenced the synthesis and release of TFPI in endothelial cells, and how TFPI affected the LPL-induced hydrolysis of VLDL in vitro and at the endothelial surface. A spontaneously transformed immortal endothelial cell line (ECV304) and primary coronary artery cells (CoEc) were used, and VLDL was isolated from healthy volunteers by density gradient ultracentrifugation. Sequential free fatty acid (FFA) measurements were used to evaluate the kinetics of the LPL-induced hydrolysis. The levels of TFPI mRNAs in the stimulated cells were determined by quantitative real-time reverse transcription-ploymerase chain reaction (qPCR) using the ABI PRISM 7700 Sequence Detection System. Stimulation of ECV304 cells for 24 hours with native VLDL (0-100 microg/mL) caused a dose-dependent increase of TFPI in the medium (6.7-23.8 ng/10(6) cells, P < 0.001), without affecting the cellular content of TFPI. The expression of TFPI mRNA was significantly upregulated after 10 minutes of stimulation with n-VLDL. Both recombinant TFPI (r-TFPI) and LPL showed a dose-dependent binding to ECV 304 cells without saturation, and no competitive binding interactions between LPL and TFPI were observed at the endothelial surface. The addition of increasing concentrations of r-TFPI to ECV 304 cells, preincubated with LPL, did not affect the hydrolysis of VLDL triglycerides. The maximal reaction velocity (V(max)) of LPL-induced hydrolysis of n-VLDL was not affected by the addition of increasing concentrations of r-TFPI to the reaction mixture in vitro. The current experimental study indicates an upregulation of TFPI synthesis and release by VLDL. LPL-induced hydrolysis of VLDL in vitro was not influenced by TFPI neither in suspension nor at the endothelial surface.

A previous study established that 2,2',4,4',5,5'-hexabromobiphenyl (HBB) entered 3T3L1 adipocytes in culture by passive diffusion from the surrounding medium. The extent to which HBB accumulated within the cell was mediated by the level of triglyceride in the cell. The present study was concerned with the conditions that would facilitate HBB removal from adipocytes as part of a continuing effort to establish an effective and safe technology for reducing body burdens of lipophilic xenobiotics. Addition of human lipoprotein to the culture medium increased HBB removal from preloaded adipocytes 18 to 80 times more than did the addition of other blood proteins. Lipoproteins also decreased equilibrium deposition of HBB in the cells. The order of effect was low-density lipoprotein (LDL) much greater than high-density lipoproteins (HLD) greater than very-low-density lipoproteins (VLDL). These results are consistent with the hypothesis that lipoproteins act as a depot by binding HBB to immobilize the xenobiotic in the medium. The rate of removal of HBB was correlated with concentrations of lipoprotein cholesterol, cholesterol ester, and phospholipid in the culture medium (r greater than .95). Total lipoprotein fractions from individuals with high levels of serum cholesterol significantly increased HBB removal from preloaded adipocytes when compared with lipoproteins from normal human serum. Decreased removal was observed with lipoproteins from individuals with low serum cholesterol or triglyceride. These results suggest that cholesterol and/or cholesterol esters in the blood play an important role in both delivery and removal of HBB from the adipose tissue. Evidence has been presented that supports the hypothesis that HBB moves freely across the adipocyte membrane and is sequestered in either the cell or pseudoblood according to its relative solubility in these compartments.

Physical activity was recorded as walking in kilometers per week during leisure time and at work in a random sample of 1205 Athenian adults and was correlated to the coronary heart disease (CHD) risk factors. In general, a low level of physical activity was found in daily life. In particular, 53% of the men and 73% of the women examined walked less than 7 km/week. No difference in walking distance was observed among the 10-year age groups, for both sexes. In men, the logarithm (log) of walking was significantly correlated with log triglycerides (r = -0.0971, p = 0.0185), total lipids (r = +0.0927, p = 0.0246), high density lipoprotein-cholesterol (HDL-C) concentration in mg/dl (r = +0.0842, p = 0.0409), very low density lipoprotein-cholesterol (VLDL-C) concentration in mg/dl (r = -0.1149, p = 0.0052), alpha-lipoproteins as percentage of total lipoproteins (r = +0.0809, p = 0.0497) and pre-beta-lipoproteins as percentage of total lipoproteins (r = -0.1024, p = 0.0129). In women, respectively, log walking was significantly correlated with age (r = -0.1318, p = 0.0011), body mass index (BMI) (r = -0.1459, p = 0.0003), maximal heart rate (r = +0.1181, p = 0.0281), diastolic blood pressure (r = -0.1153, p = 0.0043), cigarette smoking (r = -0.810, p = 0.0448), log triglycerides (r = -0.1468, p = 0.0003), total lipids (r = -0.1415, p = 0.0004), VLDL-cholesterol concentration in mg/dl (r = -0.1475, p = 0.0002), total/HDL cholesterol ratio (r = -0.0968, p = 0.0165), alpha-lipoproteins as percentage of total lipoproteins (r = +0.1141, p = 0.0047), pre-beta-lipoproteins as percentage of total lipoproteins (r = -0.1324, p = 0.0010), urea (r = -0.1035, p = 0.0107) (r = +0.01221, p = 0.0107) and uric acid (r = -0.1221, p = 0.0026). Using a stepwise multiple linear regression analysis model, it was found that log walking was significantly and independently associated with alpha-lipoproteins as percentage of total lipoproteins in men (positive association) and with BMI in women (negative association).

To explore the functions of very low density lipoprotein receptor (VLDL-R) subtype II in lipoprotein metabolism and foam cells formation, the recombinant plasmid with the two subtypes cDNA was constructed respectively, the 1dl-A7 cell lines were transfected and two cell lines expressing VLDL-R were obtained: one stably expressing the VLDLR with the O-linked sugar region (type I VLDLR) and the other without the O-linked sugar region (type II VLDLR). In the study on binding of VLDLR to their nuclein labeled natural ligands (VLDL and beta-VLDL), it was found that surface binding of 25 I-VLDL or 125 I-beta-VLDL of 1dl-A7 cells transfected with type I VLDL R recombinant (1dl-A7-VRI) was more higher than that of 1dl-A7 cells transfected with type II VLDLR recombinant (1dl-A7-VRII). After being incubated with VLDL for different time, the contents of triglyceride and total cholesterol in cells were mensurated, and the formation of foam cells and accumulation of lipid in cells was observed by oil-red O staining. The results showed that the contents of triglyceride and total cholesterol in 1dl-A7-VR I were much higher than those in 1dl-A7-VR II, and 1dl-A7-VR I could transform into foam cells notably. It was suggested that type I VLDLR binds with relative higher affinity to VLDL and beta-VLDL, and internalizes much more lipoprotein into cells. As a result, we can conclude that type I VLDLR plays a more important role in lipoprotein metabolism and foam cells formation than type II VLDLR.

The present work studies lipid metabolism in patients with algodystrophy (AD). A correct positive correlation (r = 0.75) between the triglyceride levels and low density lipoprotein (LDL)/very low density lipoprotein (VLDL) ratio and the VLDL increase observed by gel disk electrophoresis confirm that a type IV hyperlipoproteinemia is associated with AD. In contrast, the degree of high density lipoprotein (HDL) saturation in cholesterol (HDL-cholesterol/HDL-phospholipids) and the classical atherogenous index (cholesterol/HDL-cholesterol) were not modified. The decrease of plasma post-heparin lipolytic activities (PHLA) was not significant but further studies should be performed to correlate PHLA with a reduced activity of the adipose tissue lipoprotein lipase.

1. Apolipoprotein B-100 (ApoB) is the principal structural and functional protein of the pro-atherogenic lipoproteins. Elevated plasma apoB is an independent risk factor for coronary artery disease. In the present study we aimed to assess the factors that determine the kinetics of apoB in the very low-density lipoprotein (VLDL) in healthy men. 2. We studied 17 non-obese men who were consuming an ad libitum diet and had the following characteristics: mean (+/-SD) age 45.5 +/- 9.7 years, body mass index (BMI) 25.1 +/- 1.4 kg/m2, waist:hip ratio 0.91 +/- 0.04, serum cholesterol 5.2 +/- 0.6 mmol/L, triglycerides 1.08 +/- 0.53 mmol/L and high-density lipoprotein-cholesterol 1.24 +/- 0.31 mmol/L. Daily dietary intake was as follows: total fat 76 +/- 26 g, carbohydrate 238 +/- 67 g, protein 103 +/- 33 g and alcohol 20 +/- 16 g. 3. The kinetics of VLDL ApoB were studied using a primed, constant infusion (1 mg/kg per h) of 1-[13C]-leucine over 8 h with measurement of isotopic enrichment of ApoB using gas chromatography/mass spectrometry. The fractional turnover rate of VLDL ApoB was estimated using a monoexponential function. The mean (+/-SD) absolute hepatic secretion rate (ASR) of ApoB was 8.5 +/- 4.6 mg/kg per day and the fractional catabolic rate (FCR) was 7.9 +/- 5.6 pools/day. The ASR was significantly correlated with the waist:hip ratio (r = 0.60; P = 0.04), but not with age, BMI, weight or nutrient intake. The FCR was significantly and inversely correlated with plasma triglycerides (r = -0.53; P = 0.03) and alcohol intake (r = -0.48; P = 0.05). 4. In conclusion, the hepatic secretion of VLDL ApoB in nonobese, healthy men is primarily determined by the waist:hip ratio, a measure of visceral fat. This is consistent with the hypothesis that the rate of lipid substrate supply in the liver regulates the output of ApoB. The fractional catabolism of VLDL ApoB may, however, be inversely related to alcohol intake and appears to determine the plasma concentration of triglycerides.

Patients with familial dysbetalipoproteinemia (FD) associated with the apo E2/2 phenotype exhibit a marked interindividual variability in serum cholesterol and triglyceride concentrations. It has been proposed that this variability is due to a combination of the apo E2/2 phenotype and additional genetic factors implicated in diseases like familial hypercholesterolemia, familial combined hyperlipoproteinemia, and familial hypertriglyceridemia. To further explore the nature of this variability, the lipoprotein profiles of 17 patients with FD associated with the apo E2/2 phenotype were analyzed by a density-gradient ultracentrifugation technique and by 2-16% polyacrylamide gel electrophoresis. It was found that all patients with FD were characterized by 1) markedly increased cholesterol concentrations of large very low density lipoprotein (VLDL) (VLDLrsus 0.08 +/- 0.03 mmol/L), small VLDL (VLDLrsus 0.27 +/- 0.13 mmol/L), and intermediate density lipoprotein (IDL) (2.25 +/- 0.72 versus 0.39 +/- 0.16 mmol/L); 2) decreased low density lipoprotein (LDL) cholesterol level (1.84 +/- 0.54 versus 3.36 +/- 0.53 mmol/L); and 3) altered composition (enrichment by cholesteryl ester) of VLDLVLDLred with normolipidemic control subjects. The cholesterol levels of IDL and LDL showed minor interindividual variabilities and were not correlated with serum cholesterol and triglyceride levels. The compositions of VLDLVLDLre independent of the concentrations of lipids in serum. However, the cholesterol concentrations of VLDLVLDLrable interindividual variabilities and were positively correlated with the serum cholesterol concentration (r = 0.84 and r = 0.95, respectively, both p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid peroxide levels and plasma lipids were studied in plasma lipoprotein fractions of streptozotocin diabetic rats, spontaneous hypertensive rats (SHR) + diabetes, and in myocardial infarction rats (MIR) + diabetes. The duration of diabetes in all experimental groups was 2.5 months. We found a tendency of elevation of cholesterol in VLDL and fall in HDL2 but the differences were not significant. Total plasma triglycerides were increased in the three diabetic groups, and the increase was due to LDL fraction but again the differences were not significant. The lipid peroxide (LP) level in total plasma showed a significant increase in the three diabetic groups: in Wistar diabetic rats LP increased 3 times, in MIR + diabetes 3.5 times, and in SHR + diabetes 5 times. The increase of LP in the three diabetic groups was due to LDL with good correlation (r = 0.60) between LP and triglycerides in LDL of the three diabetic groups. The results are in agreement with the concept of the importance of lipoprotein fraction changes: increased cholesterol, triglycerides and lipid peroxides in atherogenic (VLDL and LDL) fractions, and decreased levels in antiatherogenic (HDL, HDL2) fractions in diabetes mellitus.

BACKGROUND

It has been shown previously that morning cortisol levels decline after oral glucose, but no report has been published regarding the changes in serum cortisol in relation to insulin sensitivity or degree of obesity.

METHODS

We studied the effects of oral glucose during a standard oral glucose tolerance test on cortisol levels in 7 obese subjects (body mass index (BMI) 29.7 +/- 3.3 kg/m2) and in 8 control subjects (BMI 24.9 +/- 3.2 kg/m2). Cortisol concentrations were normalized to time 0 because of wide between subject variation. On another day, a frequently sampled intravenous glucose tolerance test with minimal model analysis was performed, obtaining the insulin sensitivity index (SI). Anthropometric measurements included different skinfolds and bioelectric impedance.

RESULTS

The waist-to-hip ratio (WHR) was similar between the 2 groups, but abdominal skinfold was significantly higher in the obese group (OG) (158.8 +/- 42.9 vs. 113.6 +/- 27.7, P = 0.03). Fat mass, percentage of fat mass, triceps and subscapular skinfolds, systolic and diastolic blood pressure, VLDL-cholesterol, total triglycerides and VLDL-triglycerides were slightly higher in the obese group (OG). Area under the curve for glucose (AUCg) after OGTT was also significantly higher in OG (9.9 +/- 2.4 vs. 7.1 +/- 0.5 mmol/l, P = 0.02) in contrast to area under the curve for insulin (102 +/- 60 vs. 73.8 +/- 26.7 mU/l, P = NS), or glucose effectiveness (0.015 +/- 0.004 vs. 0.015 +/- 0.009 min-1, P = NS). Subjects with the highest WHR of both groups exhibited a greater cortisol suppression (56 +/- 0.09 vs. 41 +/- 0.17, P = 0.05). Normalized serum cortisol after OGTT was significantly lower from minute 60 to 120 in the OG (P = 0.001, 0.003 and 0.01 at 60, 90 and 120 minutes, respectively). The maximal cortisol suppression was 59.2% in the OG in comparison with 43% in the control group (P = 0.027). This maximal cortisol suppression correlated weakly with the maximal insulin response after oral glucose (r = 0.49, P = 0.07). In a multiple linear regression analysis, with maximal cortisol suppression as dependent variable, both BMI (P = 0.03) and SI (0.02) contributed to the variance of maximal cortisol suppression (R2 = 0.40).

CONCLUSIONS

We show that differences in cortisol decline are at least partially attributed to differences in insulin sensitivity and to differences in abdominal fat. This abdominal-related decrease of cortisol might support the concept that the increased visceral adipose tissue mass with a high density of glucocorticoid receptors enhances the metabolism of cortisol. Perhaps the subjects with higher abdominal fat or insulin resistance are prone to lower cortisol levels after carbohydrate-rich intakes in the morning. These lower cortisol levels, behaving as a positive feed-back signal, might generate higher ACTH and cortisol responses after protein-rich meals at mid-day.

The hypothesis is that poly-(R)-3-hydroxybutyrates (PHB), linear polymers of the ketone body, R-3-hydroxybutyrate (R-3HB), are atherogenic components of lipoprotein Lp(a). PHB are universal constituents of biological cells and are thus components of all foods. Medium chain-length PHB (<200 residues) (mPHB) are located in membranes and organelles, and short-chain PHB (<15 residues) are covalently attached to certain proteins (cPHB). PHB are highly insoluble in water, but soluble in lipids in which they exhibit a high intrinsic viscosity. They have a higher density than other cellular lipids and they are very adhesive, i.e. they engage in multiple noncovalent interactions with other molecules and salts via hydrogen, hydrophobic and coordinate bonds, thus producing insoluble deposits. Following digestive processes, PHB enter the circulation in chylomicrons and very low density lipoproteins (VLDL). The majority of the PHB (>70%) are absorbed by albumin, which transports them to the liver for disposal. When the amount of PHB in the diet exceed the capacity of albumin to safely remove them from the circulation, the excess PHB remain in the lipid core of LDL particles that become constituents of lipoprotein Lp(a), and contribute to the formation of arterial deposits. In summary, the presence of PHB – water-insoluble, dense, viscous, adhesive polymers – in the lipid cores of the LDL moieties of Lp(a) particles supports the hypothesis that PHB are atherogenic components of Lp(a).

VLDL cholesterol concentrations were determined in 1641 male and 608 female and VLDL apolipoprotein B concentrations in 505 male and 211 female company employees in Westphalia aged 17-70 years. VLDL cholesterol and VLDL apolipoprotein B values were found to be distributed with positive skew in both sexes but were higher in men than in women (median in men: VLDL cholesterol 0.30 mmol/l, VLDL apolipoprotein B 0.066 g/l, median in women: VLDL cholesterol 0.18 mmol/l, VLDL apolipoprotein B 0.047 g/l). In males VLDL cholesterol and VLDL apolipoprotein B were closely correlated to each other (r = 0.757) as well as to triacylglycerols (VLDL cholesterol: r = 0.673, VLDL apolipoprotein B: r = -0.419). In females these observed correlations were weaker. The VLDL cholesterol/VLDL apolipoprotein B ratio was also higher in men (median 4.28 mmol/g) than in women (median 3.15 mmol/g). The ratio correlated to triacylglycerols (men: r = 0.591, women: r = 0.321). The results suggest that the composition of VLDL may be related to triacylglycerols in serum.

BACKGROUND

The importance of serum triacylglycerols (TG) as a risk factor of cardiovascular complications in non-insulin-dependent diabetes mellitus (NIDDM) patients has been emphasized in recent studies.

OBJECTIVE

In the study of our group of NIDDM patients with and without coronary artery disease (CAD), it has been expedient to follow: 1. the difference in their serum TG, VLDL lipoprotein, total, HDL and LDL cholesterol levels, 2. dependence of other parameters on TG, 3. to answer the question as to what extent the lowering of TG in NIDDM patients is expected to be decreasing the risk of CAD.

METHODS

The investigated groups included the total of 39 NIDDM out-patients; 20 with manifest signs of CAD. The lipoproteins were measured using the BIO-LACHEMAR kits.

CONCLUSIONS

In CAD group, the serum TG and VLDL were significantly increased, HDL cholesterol being lower (p < 0.01, p < 0.01, p < 0.02, respectively). The TG-to-HDL cholesterol, TG-to-total cholesterol ratios and atherogenic index (= total cholesterol-to-HDL cholesterol ratio) were in the CAD group also significantly higher (p < 0.02, p < 0.02 and p < 0.002, respectively). Furthermore, the serum TG was positively correlated with the atherogenic index and LDL (p < 0.001 and p < 0.05; r = 0.603 and r = 0.397, respectively). The logarithm of TG was a strong positive correlate of the total cholesterol (p < 0.001; r = 0.584). On the other hand, the serum TG was negatively correlated with HDL cholesterol (p < 0.005; r = -0.466). When logarithm of TG was taken, the statistical significance of all these correlations was even higher. The serum TG levels were significantly higher in patients with CAD. (Tab. 2, Fig. 7, Ref. 10.)

Low birth weight was associated with cardiometabolic diseases in adult age. Insulin-like growth factor-1 (IGF-1) has a crucial role in fetal growth and also associates with cardiometabolic risks in adults. Therefore, we elucidated the association between IGF-1 level and serum lipids in cord blood of preterm infants. The subjects were 41 consecutive, healthy preterm neonates (27 male, 14 female) born at <37-week gestational age, including 10 small for gestational age (SGA) infants (<10th percentile). IGF-1 levels and serum lipids were measured in cord blood, and high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and very low-density lipoprotein triglyceride (VLDLTG) levels were determined by HPLC method. SGA infants had lower IGF-1 (13.1 ± 5.3 ng/ml), total cholesterol (TC) (55.0 ± 14.8), LDLC (21.6 ± 8.3) and HDLC (26.3 ± 11.3) levels, and higher VLDLTG levels (19.0 ± 12.7 mg/dl) than in appropriate for gestational age (AGA) infants (53.6 ± 25.6, 83.4 ± 18.9, 36.6 ± 11.1, 38.5 ± 11.6, 8.1 ± 7.0, respectively). In simple regression analyses, log IGF-1 correlated positively with birth weight (r = 0.721, P < 0.001), TC (r = 0.636, P < 0.001), LDLC (r = 0.453, P = 0.006), and HDLC levels (r = 0.648, P < 0.001), and negatively with log TG (r = -0.484, P = 0.002) and log VLDL-TG (r = -0.393, P = 0.018). Multiple regression analyses demonstrated that IGF-1 was an independent predictor of TC, HDLC and TG levels after the gestational age and birth weight were taken into account. In preterm SGA infants, cord blood lipids profile altered with the concomitant decrease in IGF-1 level.

OBJECTIVE

To explore the association between serum lipoprotein lipase (LPL) level and dyslipidemia in patients with obstructive sleep apnea syndromes (OSAS).

METHODS

Overnight polysomnography (PSG) was performed for 158 patients with snoring at our Sleep Center from June 2011 to April 2013. Based on the results of apnea-hypopnea index (AHI) assessment, they were divided into 4 groups: primary snoring (AHI<5/h, n = 26), mild (5/h ≤ AHI ≤ 15/h, n = 23), moderate (15/h < AHI ≤ 30/h, n = 31) and severe (AHI>30/h, n = 78) OSAS. According to body mass index (BMI), primary snoring group was further divided into normal BMI and overweight (obese) groups. The level of LPL was determined by enzyme-linked immunosorbent assay (ELISA) and the correlations were observed with OSAS, blood total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoprotein (VLDL).In normal weight OSAS patients, the relationship was analyzed between different conditions, plasma lipid and serum LPL.In 49 OSAS groups, the level of LPL was observed after 6-month continuous positive airflow pressure (CPAP).

RESULTS

From a comparison of four groups, it was found that AHI, night blood lowest oxygen saturation (L-SaO2) and time ratio of lowest SaO2<90% (TS90%) had statistical significance (all P < 0.01). The serum LPL gradually decreased in four groups. Compared with primary snoring group, there was a significant increase of serum LPL level in severe OSAS group ((37 ± 15) vs (45 ± 17) µg/L, P = 0.022). And severe OSAS group had significantly higher serum levels of TC, TG and LDL (P = 0.025,0.001,0.049).HDL of OSAS group was significantly lower than that of primary snoring group (all P < 0.05). Additionally, after adjustment for BMI and age, serum LPL levels showed significant negative correlations with TC and LDL (r = 0.221,0.199) .Serum LPL level was negative correlated with AHI and TS90 % and oxygen decrease index (ODI) (r = 0.231,0.228,0.184). Compared with normal BMI patients, there was a significant increase of VLDL ((0.77 ± 0.30) vs (0.46 ± 0.23) mmol/L, P = 0.034) and decrease of LPL ((37 ± 10) vs (523 ± 23) µg/L, P = 0.047) in weight (obesity) in primary snoring group. Compared with primary snoring group in normal BMI groups, there was a significant increase of TG,VLDL and decrease of LPL, HDL in OSAS group (all P < 0.05). The level of LPL significantly increased after 6-month CPAP ((60 ± 6) vs (38 ± 3) µg/L, P = 0.001).

CONCLUSIONS

Serum LPL and plasma lipid decrease in OSAS patients. And serum LPL level is correlated significantly with the severity of OSAS and nocturnal hypoxia. Thus LPL may play some roles in dyslipidemia of OSAS patients.

OBJECTIVE

Ectopic deposition of fat in skeletal muscle is a feature of metabolic syndrome, but its specific association with very-low-density lipoprotein (VLDL)-apolipoprotein (apo) B-100 metabolism remains unclear.

METHODS

We examined the association between skeletal muscle fat content and VLDL-apoB-100 kinetics in 25 obese subjects, and the responses of these variables to weight loss. The fat contents of liver, abdomen and skeletal muscle were determined by magnetic resonance imaging, and VLDL-apoB-100 kinetics were assessed using stable isotope tracers.

RESULTS

In obese subjects who were insulin sensitive (homeostasis model assessment, HOMA, score ≤ 2.6, n = 12), skeletal muscle fat content was significantly associated with hepatic fat content (r = 0.636), energy intake (r = 0.694), plasma triglyceride (r = 0.644), apoB-100 (r = 0.529), glucose (r = 0.622), VLDL-apoB-100 concentrations (r = 0.860), VLDL-apoB-100 fractional catabolic rate (FCR; r = -0.581) and VLDL-apoB-100 secretion rate (r = 0.607). These associations were not found in obese subjects who were insulin resistant (HOMA score >2.6, n = 13). Of these 25 subjects, 10 obese subjects underwent a 16-week weight loss program. The low-fat diet achieved significant reduction (p < 0.05) in body weight, visceral and subcutaneous fat areas, liver and skeletal muscle fat, energy intake, triglyceride, insulin, HOMA score, VLDL-apoB100 concentrations and VLDL-apoB100 secretion rate. The percentage reduction of skeletal muscle fat with weight loss was significantly associated with the corresponding changes in VLDL-apoB100 concentration (r = 0.770, p = 0.009) and VLDL-apoB-100 secretion (r = 0.682, p = 0.030).

CONCLUSIONS

Skeletal muscle fat content is associated with VLDL-apoB-100 transport. Weight loss lowers skeletal muscle fat and VLDL-apoB-100 secretion.

The close relationship between Alzheimer's disease (AD) and obesity was recognized many years ago. However, complete understanding of the pathological mechanisms underlying the interactions between degeneration of CNS and fat metabolism is still missing. The leptin a key adipokine of white adipose tissue has been suggested as one of the major mediators linking the obesity and AD. Here we investigated the association between peripheral levels of leptin, general metabolic status and stage of the pathogenesis in rat transgenic model of AD. We demonstrate significantly decreased levels of plasma leptin in animals with experimentally induced progressive neurofibrillary pathology, which represents only 62.3% (P = 0.0015) of those observed in normal wild type control animals. More detailed analysis showed a strong and statistically significant inverse correlation between the load of neurofibrillary pathology and peripheral levels of leptin (r = - 0.7248, P = 0.0177). We also observed a loss of body weight during development of neurodegeneration (about 14% less than control animals, P = 0.0004) and decrease in several metabolic parameters such as glucose, insulin, triglycerides and VLDL in plasma of the transgenic animals. Our data suggest that plasma leptin could serve as a convenient peripheral biomarker for tauopathies and Alzheimer's disease. Decrease in gene expression of leptin in fat tissue and its plasma level was found as one of the consequences of experimentally induced neurodegeneration. Our data may help to design rational diagnostic and therapeutic strategies for patients suffering from Alzheimer's disease or other forms of tauopathy.

<st<em>r</em>ong class="sub-title"> Keywo<em>r</em>ds: </st<em>r</em>ong> Leptin; Neu<em>r</em>ofib<em>r</em>illa<em>r</em>y pathology; Tau p<em>r</em>otein; T<em>r</em>ansgenic <em>r</em>at.

The concentration of five lipid-soluble antioxidants (gamma- and alpha-tocopherol, lycopene, beta-carotene and ubiquinol-10) was measured in plasma and very low-density, low-density and high-density lipoproteins (VLDL, LDL and HDL) isolated from young healthy normo- cholesterolemic subjects. Alpha-tocopherol was the exclusive antioxidant whose plasma concentration significantly correlated with the absolute concentration of total cholesterol (r =0.541, P<0.001). No correlation was found between plasma concentration and lipoprotein content of alpha-tocopherol and ubiquinol-10, whereas it reached statistically significant values for gamma-tocopherol, lycopene and beta-carotene. The alpha-tocopherol content in VLDL and HDL, but not in LDL, was strictly associated with the relative abundance of cholesterol and phospholipids in the lipoprotein particles. Moreover, the difference between alpha-tocopherol concentration in VLDL and LDL appeared to be strictly related to the differences in cholesterol, phospholipids and triglycerides. The percent distribution of the total plasma pool of antioxidant in each lipoprotein class revealed that gamma- and alpha-tocopherol were roughly equally distributed in LDL and HDL. On the other hand, lycopene, beta-carotene and ubiquinol-10 were preferentially sequestered in LDL. Finally, the absolute and relative concentration of alpha-tocopherol, but not that of other antioxidants, in HDL exhibited a statistically significant correlation with plasma HDL/LDL cholesterol ratio. These findings indicate that: (i) plasma concentrations of major lipid-soluble antioxidants are not always predictive of their levels in lipoproteins and that, within individual lipoprotein classes, (ii) the lipid composition, metabolism and relative plasma concentration may significantly affect their abundance. 2000 Academic Press@p$hr Copyright 2000 Academic Press.

The aim of this study was to define the disposition of carbamazepine (CBZ) in serum lipoproteins. The examination was conducted using the serum of 51 patients treated with carbamazepine the concentration of which was monitored 51 patients, 22 women and 29 men, 1.5-35 years old/mean 13.0 +/- 6.7 years/weighing 10.2-90.0 kg/mean 46.5 +/- 23.6/participated in the study. Every patient received carbamazepine in an individual oral dose. Concentrations of cholesterol, triglicerides, proteins and CBZ were determined. Lipoprotein fractions (VLDL, LDL, HDL and LPDS) were separated by ultracentrifugation of serum. Carbamazepine concentrations were measured by fluorescence polarization immunoassay technique on a TD x analyzer. Cholesterol, triglicerides and proteins levels were measured on Bayer--Technicon apparaturs. Carbamazepine is distributed in plasma lipoproteins, mainly in HDL fraction (mean 45.2 +/- 9.0%) and in LPDS (mean 43.2 +/- 9.3%) fraction. Ratio of carbamazepine concentration to cholesterol (RcCH), triglicerides (RcTG) and proteins concentration (RcP) and carbamazepine concentration (%) to cholesterol (R% CH), triglicerides (R% TG) and proteins concentration (%/R% P) are different in different fractions. The obtained results suggest that the disposition of CBZ in lipoprotein fractions may have a significant importance in the therapy and fat metabolism disorders make the changes of drug dose urgent.

The protein composition of apoprotein C regarding peptides CII, CIII1, and CIII2 has been studied in VLDLs in 59 normal or hypertriglyceridemic subjects. The percentages of the peptides found in each subject were correlated with serum triacylglycerol levels. There are very good correlations between the proportion of VLDL apo CII and triglyceridemia (r = -0.63) and between the proportion of CII1 and triglyceridemia (r = 0.66). The proportion of apo CII decreases as triacylglycerol level increases, whereas the proportion of apo CII1 increases under the same conditions. The percentage of apo CII2 varies in the same way as does apo CII, but to a lesser degree. The apo CII/CIII1 and apo CIII2/CIII1 ratios decrease as triglyceridemia increases. In contrast, the apo CII/CIII2 radio, though reduced, is not significantly modified. Mechanisms are reviewed that could lead to changes in apoprotein C in subjects with hyperlipoproteinemia, and the possible relationship with lipoprotein lipase activity is discussed.

Background: Hepatic de novo lipogenesis (DNL) is ideally measured in very low-density lipoprotein (VLDL)-triacylglycerol (TAG). In the fasting state, the majority of plasma TAG typically represents VLDL-TAG; however, the merits of measuring DNL in total plasma TAG have not been assessed. This study aimed to assess the performance of DNL measured in VLDL-TAG (DNL_VLDL-TAG) compared to that measured in total plasma TAG (DNL_Plasma-TAG).Methods: Using deuterated water, newly synthesised palmitate was determined in fasting plasma VLDL-TAG and total TAG in 63 subjects taking part in multiple studies resulting in n = 123 assessments of DNL (%new palmitate of total palmitate). Subjects were split into tertiles to investigate if DNL_Plasma-TAG could correctly classify subjects having 'high' (top tertile) and 'low' (bottom tertile) DNL. Repeatability was assessed in a subgroup (n = 16) with repeat visits.Results: DNL_VLDL-TAG was 6.8% (IQR 3.6-10.7%) and DNL_Plasma-TAG was 7.5% (IQR 4.0%-11.0%), and the correlation between the methods was r_s = 0.62 (p < 0.0001). Bland-Altman plots demonstrated similar performance (mean difference 0.81%, p = 0.09); however, the agreement interval was wide (-9.6% to 11.2%). Compared to DNL_VLDL-TAG, 54% of subjects with low DNL were correctly classified, whilst 66% of subjects with high DNL were correctly classified using DNL_Plasma-TAG. Repeatability was acceptable (i.e. not different) at the group level, but the majority of subjects had an intra-individual variability over 25%.Conclusion: DNL in total plasma TAG performed similarly to DNL in VLDL-TAG at the group level, but there was large variability at the individual level. We suggest that plasma TAG could be useful for comparing DNL between groups.

Lipoprotein abnormalities, mainly high very-low-density lipoprotein (VLDL) and low high-density lipoprotein (HDL) levels, increase the risk of coronary heart disease (CHD) in type II diabetic patients. To investigate the relationship between these lipoprotein abnormalities and the postprandial (PP) lipid-clearing capacity, triglyceride (TG) and hormonal levels were determined hourly up to the 4th hour after a mixed meal containing 32.5 g lipids/m2 body surface in 14 treated non-obese type II diabetic patients with adequate nutritional and glycemic control (hemoglobin A1C [HbA1C] < 7%) and in 12 healthy subjects matched for age, sex, and body mass index (BMI). Mean cholesterol levels did not differ between patients and controls, with fasting TG moderately increased in diabetics (140 +/- 70 v 66 +/- 34 mg/dL, P < .01). Whereas fasting TG levels in patients showed a continuous distribution from 55 to 250 mg/dL, postprandial TG clearly identified two different subgroups. A "high-responder" or hypertriglyceridemic subgroup (HTG) showed PP TG levels significantly higher than control levels (290 +/- 62 v 106 +/- 41 mg/dL, P < .001), with higher fasting TG as well (181 +/- 52, P < .01), whereas both fasting and PP TG levels were not different from control levels in the normotriglyceridemic (NTG) diabetic subgroup. The magnitude of the PP triglyceridemic area showed a negative correlation with HDL2 cholesterol (r = .66, P < .001) and a positive correlation with PP HDL2 TG enrichment (r = .80, P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma lipoproteins are important carriers of cholesterol and have been linked strongly to cardiovascular disease (CVD). Our study aimed to achieve fine-grained measurements of lipoprotein subpopulations such as low-density lipoprotein (LDL), lipoprotein(a) (Lp(a), or remnant lipoproteins (RLP) using electron microscopy combined with machine learning tools from microliter samples of human plasma. In the reported method, lipoproteins were absorbed onto electron microscopy (EM) support films from diluted plasma and embedded in thin films of methyl cellulose (MC) containing mixed metal stains, providing intense edge contrast. The results show that LPs have a continuous frequency distribution of sizes, extending from LDL (> 15 nm) to intermediate density lipoprotein (IDL) and very low-density lipoproteins (VLDL). Furthermore, mixed metal staining produces striking "positive" contrast of specific antibodies attached to lipoproteins providing quantitative data on apolipoprotein(a)-positive Lp(a) or apolipoprotein B (ApoB)-positive particles. To enable automatic particle characterization, we also demonstrated efficient segmentation of lipoprotein particles using deep learning software characterized by a Mask Region-based Convolutional Neural Networks (R-CNN) architecture with transfer learning. In future, EM and machine learning could be combined with microarray deposition and automated imaging for higher throughput quantitation of lipoproteins associated with CVD risk.

Keywords: apolipoprotein B; apolipoprotein(a); cardiovascular disease; electron microscopy; lipoproteins; low-density lipoproteins; machine learning; nanoparticles.

We examined the effects of the resistant starches of adzuki (Vigna angularis), kintoki (Phaseolus vulgaris, variety), and tebou (P. vulgaris, variety) beans on the lipid metabolism in rats. Rats were fed a cholesterol-free diet with 25 g of cornstarch (CS)/100 g diet, 25 g of adzuki starch (AS)/100 g diet, 25 g of kintoki starch (KS)/100 g diet, or 25 g of tebou starch (TS)/100 g diet for 4 wk. The cecal contents in the TS group were significantly higher than those in the CS and KS groups. There were no significant differences in body weight or food intake among the groups. The relative liver weight in the CS group was significantly greater than that of the AS, KS, and TS groups. The serum total cholesterol, VLDL+IDL+LDL-cholesterol, and triglyceride concentrations in the AS, KS, and TS groups were significantly lower than those in the CS group throughout the feeding period. Though the total hepatic cholesterol concentration in the TS group was significantly higher than that in the KS group, there were no significant differences between the CS and other starch groups. The cecal pH value in the CS group was significantly higher than that of the bean starch groups. The cecal butyric acid concentrations in the AS, KS, and TS groups were significantly higher than that in the CS group, and the cecal total short-chain fatty acid (SCFA) concentrations in the AS and TS groups were significantly higher than those of the CS group. The fecal cholesterol excretion of the AS, KS, and TS groups were significantly higher than that in the CS group. The fecal coprostanol excretion in the AS group was significantly higher than that in the CS group. There was a negative correlation between the serum VLDL+IDL+LDL-cholesterol concentration and fecal neutral steroid excretion (r = -0.664, p < 0.001) in the present experiment. Furthermore, the cecal total SCFA concentration was negatively correlated with the serum VLDL+IDL+LDL-cholesterol concentration (r = -0.665, p < 0.001) and positively correlated with fecal neutral steroid excretion (r = 0.481, p < 0.05). The cecal butyric acid level was also negatively correlated with the serum VLDL+IDL+LDL-cholesterol concentration (r = -0.609, p < 0.01) and positively correlated with fecal neutral steroid excretion (r = 0.658, p < 0.001). The results suggest that AS, KS, and TS elevate cecal SCFA concentration, in particular butyric acid concentration, and fecal neutral sterol excretion, and lower the serum total cholesterol level.