Plasma Lipid Transfer Protein Activity Research Articles

Relationships between changes in plasma lipid transfer proteins and apolipoprotein B-100 kinetics during fenofibrate treatment in the metabolic syndrome

The aim of the present study was to investigate the association between changes in apoB (apolipoprotein B-100) kinetics and plasma PLTP (phospholipid transfer protein) and CETP (cholesteryl ester transfer protein) activities in men with MetS (the metabolic syndrome) treated with fenofibrate. Eleven men with MetS underwent a double-blind cross-over treatment with fenofibrate (200 mg/day) or placebo for 5 weeks. Compared with placebo, fenofibrate significantly increased the FCRs (fractional catabolic rates) of apoB in VLDL (very-low-density lipoprotein), IDL (intermediate-density lipoprotein) and LDL (low-density lipoprotein) (all P<0.01), with no significant reduction (-8%; P=0.131) in VLDL-apoB PR (production rate), but an almost significant increase (+15%, P=0.061) in LDL-apoB PR. Fenofibrate significantly lowered plasma TG [triacylglycerol (triglyceride); P<0.001], the VLDL-TG/apoB ratio (P=0.003) and CETP activity (P=0.004), but increased plasma HDL (high-density lipoprotein)-cholesterol concentration (P<0.001) and PLTP activity (P=0.03). The increase in PLTP activity was positively associated with the increase in both LDL-apoB FCR (r=0.641, P=0.034) and PR (r=0.625, P=0.040), and this was independent of the fall in plasma CETP activity and lathosterol level. The decrease in CETP activity was positively associated with the decrease in VLDL-apoB PR (r=0.615, P=0.044), but this association was not robust and not independent of changes in PLTP activity and lathosterol levels. Hence, in MetS, the effects of fenofibrate on plasma lipid transfer protein activities, especially PLTP activity, may partially explain the associated changes in apoB kinetics.

Type 2 diabetes mellitus is associated with differential effects on plasma cholesteryl ester transfer protein and phospholipid transfer protein activities and concentrations

Background: Human plasma contains two lipid transfer proteins, cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), which are crucial in reverse cholesterol transport. Methods: Plasma CETP and PLTP activity levels and concentrations in 16 type 2 diabetic patients and 16 matched healthy subjects were determined, and these data were correlated to clinical variables, including insulin sensitivity and lipid levels. Results: Plasma triglycerides were higher (p<0.02) and high‐density lipoprotein (HDL) cholesterol (p<0.02) was lower in diabetic patients. Plasma CETP activity and concentrations were not significantly different between diabetic and healthy subjects, but CETP specific activity was lower in diabetic patients (p<0.001). Multiple regression analysis showed that plasma CETP activity was positively related to CETP concentration (p=0.0001) and negatively to the diabetic state (p<0.002) or to HbA1c (p<0.02). PLTP activity (p<0.05) and specific activity were higher (p<0.05), whereas there was no difference in PLTP concentration between the two groups. There was no significant bivariate correlation between PLTP concentration and activity, in either healthy or diabetic subjects. Multiple regression analysis did disclose positive relationships of PLTP activity with PLTP concentration (p=0.0001), plasma triglycerides (p=0.0001) and waist/hip ratio (p=0.0001), but not with the diabetic state or HbA1c. Conclusions: Neither CETP nor PLTP activity was independently associated with insulin sensitivity. Specific CETP activity is decreased in type 2 diabetes mellitus. In contrast, specific PLTP activity is higher in diabetes, as a result of the association of plasma PLTP activity with plasma triglycerides and obesity. Measurement of both plasma lipid transfer protein activity and mass levels may thus provide extra information in diabetes mellitus.

Higher plasma lipid transfer protein activities and unfavorable lipoprotein changes in cigarette-smoking men.

The mechanism responsible for the atherogenic lipoprotein changes associated with cigarette smoking are largely unknown. Lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of plasma cholesterol and the transfer of cholesteryl ester from high-density lipoproteins (HDLs) toward very-low- and low-density lipoproteins (VLDLs+LDLs). Another transfer factor, phospholipid transfer protein (PLTP), recently has been shown to be involved in the interconversion of HDL particles in vitro, but its physiological function is not yet clear. We measured the activities of LCAT, CETP (as cholesteryl ester exchange activity), and PLTP using exogenous substrate assays as well as lipoprotein profiles in the plasma of 21 normolipidemic cigarette-smoking men (total plasma cholesterol below 6.5 mmol/L and triglyceride below 2.5 mmol/L) and 21 individually matched nonsmoking control subjects. HDL cholesterol, HDL cholesteryl ester, and plasma apolipoprotein A-I levels were lower in the smokers than in the control subjects (P < or = .05 for all parameters). Median plasma CETP activity was 18% higher (P < .02) and median plasma PLTP activity was 8% higher (P < .05) in the smokers compared with the nonsmokers. LCAT activity was not different between the groups. HDL cholesteryl ester concentration was positively related to LCAT activity in control subjects but not in smokers. By contrast, there was an inverse relation of CETP activity with HDL cholesteryl ester in smokers but not in nonsmokers. Multiple regression analysis demonstrated that the lowering effect of smoking on HDL cholesteryl ester could be explained by its influence on CETP activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of adiposity on plasma lipid transfer protein activities: a possible link between insulin resistance and high density lipoprotein metabolism.

The mechanisms responsible for the decreased high density lipoprotein (HDL) cholesterol levels associated with obesity and insulin resistance are not well understood. Lecithin: cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) are key factors in the esterification of cholesterol in HDL and the subsequent transfer of cholesteryl ester towards apolipoprotein B-containing lipoproteins. Phospholipid transfer protein (PLTP) may be involved in the regulation of HDL particle size. We therefore measured the activities of LCAT, CETP and PLTP using exogenous substrate assays, as well as lipids, lipoproteins, insulin and C-peptide in fasting plasma from eight healthy obese men (body mass index > 27 kg m-2) and 24 non-obese subjects. The obese men had lower levels of HDL cholesterol (P < 0.05) and higher levels of plasma triglycerides (P < 0.05), insulin (P < 0.05) and C-peptide (P < 0.01), as compared to the quartile of subjects with the lowest body mass index (BMI < 22.4 kg m-2). CETP and PLTP activities were elevated in the obese men by 35% (P < 0.01) and by 15% (P < 0.05), respectively. LCAT activity was comparable among the quartiles. Linear regression analysis showed that CETP activity was positively correlated with body mass index (P < 0.02), fasting blood glucose (P < 0.05) and plasma C-peptide (P < 0.05). PLTP activity was positively related to body mass index (P < 0.01), waist to hip circumference ratio (P < 0.001), as well as to fasting blood glucose (P < 0.05) and plasma C-peptide (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Purification, characterization, and conformational analysis of rabbit plasma lipid transfer protein.

A procedure for rapid isolation of lipid transfer protein (LTP) from commercially available rabbit plasma is described. Use of protease inhibitors was important for obtaining intact, stable LTP. After lipoproteins were precipitated from the plasma by dextran sulfate, column chromatographies through Butyl-Toyopearl 650M, CM-Toyopearl 650M, and Butyl-Toyopearl 650M were employed. Overall purification from plasma was (3830 +/- 710)-fold with a yield of 3-5%. The isolated LTP migrated as a single band during sodium dodecyl sulfate-polyacrylamide gel electrophoresis with M(r) = 74K and had an NH2-terminal amino acid sequence and amino acid composition closely matching those predicted by its cDNA. This band was recognized by immunoblotting with an anti-human LTP monoclonal antibody, TP2. Gel permeation chromatography revealed that LTP behaved as a globular protein of M(r) = 83K. Isoelectric focusing of the isolated LTP demonstrated a ladder of bands with pI's of 5.7-5.9. The specific activity of rabbit LTP was similar to that of human LTP. Monoclonal antibody TP2, that blocked human plasma LTP activity almost completely, only partially inhibited purified rabbit LTP, and rabbit plasma LTP activity to a similar extent. By a centrifugation binding assay, rabbit LTP was shown to predominantly associate with lipid microemulsion in its presence. Circular dichroism spectroscopy indicated a high content of beta structure, and Provencher and Glöckner analysis gave estimated fractional values of 0.30, 0.39, 0.12, and 0.19 for alpha-helix, beta-sheet, beta-turn, and remainder content, respectively. Upon lipid binding, the helical content did not change drastically, although there was some disordering of beta structure.

Lecithin-cholesterol acyltransferase and lipid transfer protein activities in liver disease

The activities of lecithin-cholesterol acyltransferase (LCAT) and lipid transfer protein (LTP) were assayed using sensitive radioassay methods in controls (n = 113) and in patients with various liver diseases (n = 72). Plasma LCAT activity decreased with progression of hepatocellular damage. Plasma LTP activity in controls was 216 ± 68 nmol/mL/h, and there were no significant differences between controls and patients withchronic hepatitis ([CH], 193 ± 70), compensated liver cirrhosis (LC) with or without hepatocellular carcinoma ([HCC], 197 ± 48 and 193 ± 62, respectively), or decompensated liver cirrhosis ([dLC], 182 ± 65). In acute viral hepatitis, LTP activity decreased significantly; however, the degree of reduction was not as dramatic as that for LCAT. There was no correlation between LCAT and LTP activity both in controls and patients with various liver diseases. LCAT activity was positively correlated with serum albumin ( r = .52, P < .01) and cholinesterase ( r = .37, P < .01) levels, and inversely correlated with serum bilirubin level ( r = −.38, P < .01); there was no correlation between plasma LTP activity and these parameters of liver function. That plasma LTP activity did not change with hepatocellular damage may indicate that the liver in humans may not be the primary site of LTP production.

Effects of hyperlipidemias in hamsters on lipid transfer protein activity and unidirectional cholesteryl ester transfer in plasma

Experiments were performed to characterize plasma lipid transfer protein activity (LTA), and the rate of [ 3H]CE transfer from HDL to lower density lipoproteins in plasma of hamsters. Compared to rabbits, hamster plasma has about one-tenth the level of d > 1.21 LTA but a relatively high level of VLDL-triacylglycerols, and a higher fractional rate of HDL-[ 3H]CE transfer in plasma (in vitro) than predicted by the d > 1.21 LTA. Like the rat, hamster plasma contains an inhibitors(s) of LTA; the level of the inhibitor activity in d > 1.21 g/ml plasma was similar in normal and hyperlipoproteinemic hamsters. Hypertriglyceridemia in sucrose-fed hamsters did not affect LTA, cholesteryl ester transfer or the plasma level of HDL-CE. However, a comparable degree of hypercholesterolemia was associated with a 122% increase in plasma d > 1.21 LTA and a 63% increase in the fractional rate of [ 3H]CE transfer from HDL to lower density lipoproteins in plasma. Cholesterol feeding in hamsters was associated with increased plasma levels of LDL-cholesterol and, to a lesser extent, with VLDL- and IDL-cholesterol.

Plasma lipid transfer activities in hyper-high-density lipoprotein cholesterolemic and healthy control subjects

The relationships between plasma lipid transfer protein (LTP) activity and various lipid or lipoprotein concentrations were studied in 14 hyper-high-density lipoprotein (hyper-HDL) cholesterolemic subjects and 152 healthy controls. We measured plasma LTP activity by our sensitive assay method, using radiolabeled proteoliposomes as the lipid donor, low-density lipoprotein (LDL) as the acceptor, and a very small amount of untreated plasma (typically 1 to 2 μL) as the sample. Control subjects had the mean of LTP activity at 206 ± 45 nmol/mL/h. The difference of LTP activity between men and women was not statistically significant. In the control subjects, the activity of plasma LTP had a significantly positive correlation with the concentrations of total cholesterol ( r = .639, P < .01) and LDL cholesterol ( r = .634, P < .01), but not with those of HDL cholesterol and total triglyceride, nor with percent ideal body weight. One of 14 patients with hyper-HDL cholesterolemia had no detectable LTP activity, and three others had very low LTP activity. From these data, LTP activity may be one of the important factors to influence plasma LDL concentration, and the lack of LTP activity may be related to a subclass of hyper-HDL cholesterolemias.

Effects of blocking plasma lipid transfer protein activity in the rabbit

Plasma lipid transfer protein activity was completely blocked in rabbits for up to 48 h by infusion with goat antibody to rabbit lipid transfer protein. Lipid transfer protein activity in plasma of control animals, infused with antibody from a non-immune goat, decreased during the experiment but was never less than 50% of pre-infusion levels. During the period that lipid transfer protein activity was completely blocked, there were changes in high-density lipoprotein composition (expressed as % by weight) with a reduction in triacylglycerol from 8.4 ± 2.4% to 1.0 ± 0.2% ( P < 0.05) and an increase in esterified cholesterol from 10.7 ± 1.7% to 14.5 ± 0.3% ( P < 0.1). In conjunction with the observed changes in high-density lipoprotein composition, there was an increase in high-density lipoprotein particle size from a mean radius of 4.7 to 5.4 nm. The change in composition and particle size was not observed in high-density lipoproteins from control animals. There was a change in the distribution of plasma cholesterol in control animals, with a fall in the proportion of cholesterol in high-density lipoproteins ( P < 0.02) and consequently an increase in the proportion of cholesterol in low-density lipoproteins ( P < 0.02). However, the distribution of plasma cholesterol in animals in which lipid transfer protein activity was inhibited was maintained at original levels during the period of inhibition. Consequently, in these animals, there was a less atherogenic distribution of cholesterol during the period of lipid transfer protein inhibition when compared with control animals. The changes observed in lipoproteins, in the absence of lipid transfer protein activity, demonstrate that lipid transfer protein modifies lipoproteins in vivo and appears to contribute to a more atherogenic lipid profile.

D-Galactosamine induced hepatitis in the rabbit: Effect on lecithin:cholesterol acyltransferase activity, plasma lipid transfer protein activity and high density lipoproteins

1. 1. Hepatitis was induced in rabbits by a single intraperitoneal injection of d(+)-galactosamine-HCl (750 mg/kg body wt). 2. 2. Plasma lecithin:cholesterol acyltransferase activity fell to 5% and lipid transfer protein activity to 50% of control values 48 hr after injection. 3. 3. Discoid high density lipoprotein began to appear in plasma of treated rabbits 36 hr after injection, along with populations of high density lipoprotein (HDL) which were both smaller (radius 3.7 nm) and larger (radius 5.9 nm) than the original HDL population (radius 4.8 nm).