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1.
Plasma kinetic behavior in hyperlipidemic subjects of a lipidic microemulsion that binds to low density lipoprotein receptors 总被引:2,自引:2,他引:2
Raul C. Maranhão Ivete A. Roland Odaly Toffoletto José Antonio Ramires Romélia P. Gonçalves Carlos H. Mesquita Fulvio Pileggi 《Lipids》1997,32(6):627-633
It was previously reported that a protein-free microemulsion (LDE) with structure roughly resembling that of the lipid portion
of low density lipoprotein (LDL) was presumably taken up by LDL receptors when injected into the bloodstream. In contact with
plasma, LDE acquires apolipoproteins (apo) including apo E that would be the ligand for receptor binding. Currently, apo were
associated to LDE by incubation with high density lipoprotein (HDL). LDE-apo uptake by mononuclear cells showed a saturation
kinetics, with an apparent K
m of 13.1 ng protein/mL. LDE-apo is able to displace LDL uptake by mononuclear cells with a K
i of 11.5 ng protein/mL. LDE without apo is, however, unable to displace LDL. The uptake of 14C-HDL is not dislocated by increasing amounts of LDE-apo, indicating that HDL and LDE-apo do not bind to the same receptor
sites. In human hyperlipidemias, LDE labeled with 14C-cholesteryl ester behaved kinetically as expected for native LDL. LDE plasma disappearance curve obtained from eight hypercholesterolemic
patients was markedly slower than that from 10 control normolipidemic subjects [fractional clearance rate (FCR)=0.02±0.01
and 0.12±0.04 h−1, respectively; P<0.0001]. On the other hand, in four severely hypertriglyceridemic patients, LDE FCR was not significantly different from
the controls (0.07±0.03 h−1). These results suggest that LDE can be a useful device to study lipoprotein metabolism. 相似文献
2.
Low density lipoprotein (LDL) plasma concentration is increased in the elderly. In this group, the incidence of coronary artery
disease (CAD) is greater and LDL remains an important risk factor for CAD development. In this study, the plasma kinetics
of a cholesterol-rich emulsion that binds to LDL receptors was studied in 10-subject groups of the elderly (70±4 yr), middle-aged
(42±5 yr) and young (23±2 yr). All were normolipidemic, nonobese, nondiabetic subjects who did not have CAD. The emulsion
was labeled with 14C-cholesteryl oleate and injected intravenously into the subjects. Blood samples were drawn at regular intervals over 24 h
to determine the plasma decay curve of the emulsion radioactive label and to estimate its plasma fractional clearance rate
(FCR, in h−1). FCR of the emulsion label was smaller in elderly compared to young subjects (0.032±0.035 and 0.071±0.049 h−1, respectively; mean±SD, P<0.05). FCR of the middle-aged subjects (0.050±0.071 h−1) was intermediate between the values of the elderly and young subjects, although not statistically different from them. A
negative correlation was found between the emulsion FCR and subjects’ age (r=−0.47, P=0.008). We conclude that aging is accompanied by progressively diminished clearance of the emulsion cholesterol esters and,
by analogy, of the native LDL. 相似文献
3.
A cholesterol-rich nanoemulsion (LDE) that mimics the composition of low-density lipoprotein (LDL) acquires apoE in the plasma
and is taken-up by the cells by LDL receptors. In this study, to verify whether free cholesterol (FC) and the cholesteryl
ester (CE) components of LDL are taken-up differently by the vessels. LDE labeled with 3H-cholesterol and 14C-cholesteryl oleate was injected into 20 coronary artery disease patients 24 h before a scheduled myocardial coronary artery
bypass grafting. The plasma kinetics of both radiolabels was determined from plasma samples collected over 24 h, and fragments
of vessels discarded during surgery were collected and analyzed for radioactivity. LDE FC was removed faster than CE. The
radioactive counting of LDE CE was greater than that of LDE FC in the blood, but the uptake of FC was markedly greater than
that of CE in all fragments: fivefold greater in the aorta (p = 0.04), fourfold greater in the internal thoracic artery (p = 0.03), tenfold greater in the saphenous vein (p = 0.01) and threefold in the radial artery (p = 0.05). In conclusion, the greater removal from plasma of FC compared with CE and the remarkably greater vessel tissue uptake
of FC compared with CE suggests that, in the plasma, FC dissociates from the nanoemulsion particles and precipitates in the
vessels. Considering LDE as an artificial nanoemulsion model for LDL, our results suggest that dissociation of FC from lipoprotein
particles and deposition in the vessel wall may play a role as an independent mechanism in atherogenesis. 相似文献
4.
Tissue Uptake Mechanisms Involved in the Clearance of Non-Protein Nanoparticles that Mimic LDL Composition: A Study with Knockout and Transgenic Mice
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Lipid core nanoparticles (LDE) resembling LDL behave similarly to native LDL when injected in animals or subjects. In contact with plasma, LDE acquires apolipoproteins (apo) E, A‐I and C and bind to LDL receptors. LDE can be used to explore LDL metabolism or as a vehicle of drugs directed against tumoral or atherosclerotic sites. The aim was to investigate in knockout (KO) and transgenic mice the plasma clearance and tissue uptake of LDE labeled with 3H‐cholesteryl ether. LDE clearance was lower in LDLR KO and apoE KO mice than in wild type (WT) mice (p < 0.05). However, infusion of human apoE3 into the apoE KO mice increased LDE clearance. LDE clearance was higher in apoA‐I KO than in WT. In apoA‐I transgenic mice, LDE clearance was lower than in apoA‐I KO and than in apoA‐I KO infusion with human HDL. Infusion of human HDL into the apoA‐I KO mice resulted in higher LDE clearance than in the apoA‐I transgenic mice (p < 0.05). In apoA‐I KO and apoA‐I KO infused human HDL, the liver uptake was greater than in WT animals and apoA‐I transgenic animals (p < 0.05). LDE clearance was lower in apoE/A‐I KO than in WT. Infusion of human HDL increased LDE clearance in those double KO mice. No difference among the groups in LDE uptake by the tissues occurred. In conclusion, results support LDLR and apoE as the key players for LDE clearance, apoA‐I also influences those processes. 相似文献
5.
The Expression of Lipoprotein Receptors Is Increased in the Infarcted Area After Myocardial Infarction Induced in Rats With Cardiac Dysfunction
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Aline D. de Lima Maria C. Guido Elaine R. Tavares Priscila O. Carvalho Alyne F. Marques Marcelo D. T. de Melo Vera M. C. Salemi Roberto Kalil‐Filho Raul C. Maranhão 《Lipids》2018,53(2):177-187
Left ventricular (LV) remodeling after myocardial infarction constitutes the structural basis for ventricular dysfunction and heart failure. The characterization underlying the expression of lipoprotein receptors in cardiac dysfunction is scarcely explored. The aim of this study was to analyze the status of lipoprotein receptors on the infarcted and noninfarcted areas of LV and to verify whether nanoparticles that mimic the lipid structure of low‐density lipoprotein (LDL) and have the ability to bind to LDL receptors (LDE) are taken up more avidly by the noninfarcted LV. 13 male Wistar rats with left coronary artery ligation (myocardial infarction [MI]) and 12 animals with SHAM operation (SHAM) were used in this study. 6 weeks after the procedure, the quantification of low‐density lipoprotein receptor (LDLR), LDL receptor‐related protein 1 (LRP1), scavenger receptor‐class B type I (SR‐BI) lipoprotein receptors, and PCNA proliferation marker, and tissue uptake of radioactively labeled LDE were performed. Immunohistochemistry and Western blot analysis showed that LDLR, LRP1, SR‐BI, and PCNA, expression in infarcted area of MI was remarkably higher than SHAM and noninfarcted subendocardial (SEN) and interstitial (INT) areas. In addition, in SEN noninfarcted area of MI, the presence of LDLR was about threefold higher than in SHAM SEN and INT noninfarcted areas. The LDE uptake of noninfarcted LV of MI group was about 30% greater than that of SHAM group. In conclusion, these findings regarding the status of lipoprotein receptors after MI induction could help to establish mechanisms on myocardial repairing. In conclusion, infarcted rats with LV dysfunction showed increased expression of lipoprotein receptors mainly in the infarcted area. 相似文献
6.
Surendra P. Verma Jean R. Philippot Bernard Bonnet Josette Sainte-Marie Yves Moschetto Donald F. H. Wallach 《Lipids》1985,20(12):890-896
Raman and resonance Raman spectra of plasma lipoproteins ± malondialdehyde were studied at concentrations which block the
normal receptor-mediated uptake by cells. The strong resonance Raman bands at about 1010, 1162 and 1530 cm−1, due to the presence of carotenoids in the lipoproteins, are envisaged as structural probes. High resolution resonance Raman
spectra of the 1500–1600 cm−1 region reveal multiple features suggesting the coexistence of several structural populations of β-carotene whose precise
assignment is complex. When plasma lipoproteins are reacted with malondialdehyde, a complex change occurs in the resonance
Raman banding of β-carotene in the 1500–1600 cm−1 region. Malonaldehyde (MDA) also modifies the acoustical region (70–200 cm−1 of low density lipoprotein (LDL) lipids. We suggest that malondialdehyde association with plasma lipoproteins alters the
lipid structure via apoprotein or apoprotein/lipid associations. 相似文献
7.
Plasma kinetics of free and esterified cholesterol in familial hypercholesterolemia: Effects of simvastatin 总被引:1,自引:1,他引:0
The objective of this study was to evaluate the kinetics of both free and esterified forms of cholesterol contained in a emulsion
that binds to LDL receptors (LDE) in subjects with heterozygous familial hypercholesterolemia (FH), and the same subjects
under the effects of high-dose simvastatin treatment, as compared with a control normolipidemic group (NL). Twentyone FH patients
(44.0±13.0 yr, 12 females, LDL cholesterol levels 6.93±1.60 mmol/L) and 22 normolipidemic patients (44.0±15.0, 10 females,
LDL cholesterol levels 3.15±0.62 mmol/L) were injected intravenously with 14C-cholesteryl ester and 3H-cholesterol. FH patients were also evaluated after 2 mon of 40 or 80 mg/d simvastatin treatment, and plasma samples were
collected over 24 h to determine the residence time (RT, in h) of both LDE labels, expressed as the median (25%; 75%). The
RT of both 14C-cholesteryl ester and 3H-cholesterol were greater in FH than in NL [FH: 36.0 (20.5; 1191.0), NL: 17.0 (12.0–62.5), P=0.015; and FH: 52.0 (30.0; 1515.0); NL 20.5 (14.0–30.0) P<0.0001]. Treatment reduced LDL cholesterol by 36% (P<0.0001), RT of 14C-cholesteryl ester by 49% (P=0.0029 vs. baseline), and 3H-cholesterol RT by 44% (P=0.019 vs. baseline). After treatment, the RT values of 14C-cholesteryl ester in the FH group approached the NL values (P=0.58), but the RT of 3H-cholesterol was still greater than those for the NL group (P=0.01). The removal of LDE cholesteryl esters and free cholesterol was delayed in FH patients. Treatment with a high dose
of simvastatin normalized the removal of cholesterol esters but not the removal of free cholesterol. 相似文献
8.
Effects of dietary phenolic compounds on tocopherol, cholesterol, and fatty acids in rats 总被引:5,自引:0,他引:5
The effects of the phenolic compounds butylated hydroxytoluene (BHT), sesamin (S), curcumin (CU), and ferulic acid (FA) on
plasma, liver, and lung concentrations of α- and γ-tocopherols (T), on plasma and liver cholesterol, and on the fatty acid
composition of liver lipids were studied in male Sprague-Dawley rats. Test compounds were given to rats ad libitum for 4 wk at 4 g/kg diet, in a diet low but adequate in vitamin E (36 mg/kg of γ-T and 25 mg/kg of α-T) and containing 2 g/kg
of cholesterol. BHT significantly reduced feed intake (P<0.05) and body weight and increased feed conversion ratio; S and BHT caused a significant enlargement of the liver (P<0.001), whereas CU and FA did not affect any of these parameters. The amount of liver lipids was significantly lowered by
BHT (P<0.01) while the other substances reduced liver lipid concentrations but not significantly. Regarding effects on tocopherol
levels, (i) feeding of BHT resulted in a significant elevation (P<0.001) of α-T in plasma, liver, and lung, while γ-T values remained unchanged; (ii) rats provided with the S diet had substantially
higher γ-T levels (P<0.001) in plasma, liver, and lung, whereas α-T levels were not affected; (iii) administration of CU raised the concentration
of α-T in the lung (P<0.01) but did not affect the plasma or liver values of any of the tocopherols; and (iv) FA had no effect on the levels of
either homolog in the plasma, liver, or lung. The level of an unknown substance in the liver was significantly reduced by
dietary BHT (P<0.001). BHT was the only compound that tended to increase total cholesterol (TC) in plasma, due to an elevation of cholesterol
in the very low density lipoprotein + low density lipoprotein (VLDL+LDL) fraction. S and FA tended to lower plasma total and
VLDL+LDL cholesterol concentrations, but the effect for CU was statistically significant (P<0.05). FA increased plasma high density lipoprotein cholesterol while the other compounds reduced it numerially, but not
significantly. BHT, CU, and S reduced cholesterol levels in the liver TC (P<0.001) and percentages of TC in liver lipids (P<0.05). With regard to the fatty acid composition of liver lipids, S increased the n-6/n-3 and the 18∶3/20∶5 polyunsaturated
fatty acids (PUFA) ratios, and BHT lowered total monounsaturated fatty acids and increased total PUFA (n−6+n−3). The effects
of CU and FA on fatty acids were not highly significant. These results suggest some in vivo interactions between these phenolic compounds and tocopherols that may increase the bioavailability of vitamin E and decrease
cholesterol in rats. 相似文献
9.
This experiment was designed to evaluate the effects of dietary red wine phenolic compounds (WP) and cholesterol on lipid
oxidation and transport in rats. For 5 wk, weanling rats were fed polyunsaturated fat diets (n−6/n−3=6.4) supplemented or
not supplemented with either 3 g/kg diet of cholesterol, 5 g/kg diet of WP, or both. The concentrations of triacylglycerols
(TAG, P<0.01) and cholesterol (P<0.0002) were reduced in fasting plasma of rats fed cholesterol despite the cholesterol enrichment of very low density lipoprotein
+ low density lipoprotein (VLDL+LDL). The response was due to the much lower plasma concentration of high density lipoprotein
(HDL) (−35%, P<0.0001). In contrast, TAG and cholesteryl ester (CE) accumulated in liver (+120 and +450%, respectively, P<0.0001). However, the cholesterol content of liver microsomes was not affected. Dietary cholesterol altered the distribution
of fatty acids mainly by reducing the ratio of arachidonic acid to linoleic acid (P<0.0001) in plasma VLDL+LDL (−35%) and HDL (−42%) and in liver TAG (−42%), CE (−78%), and phospholipids (−28%). Dietary WP
had little or no effect on these variables. On the other hand, dietary cholesterol lowered the α-tocopherol concentration
in VLDL+LDL (−40%, P<0.003) and in microsomes (−60%, P<0.0001). In contrast, dietary WP increased the concentration in microsomes (+21%, P<0.0001), but had no effect on the concentration in VLDL+LDL. Cholesterol feeding decreased (P<0.006) whereas WP feeding increased (P<0.0001) the resistance of VLDL+LDL to copper-induced oxidation. The production of conjugated dienes after 25 h of oxidation
ranged between 650 (WP without cholesterol) and 2,560 (cholesterol without WP) μmol/g VLDL+LDL protein. These findings show
that dietary WP were absorbed at sufficient levels to contribute to the protection of polyunsaturated fatty acids in plasma
and membranes. They could also reduce the consumption of α-tocopherol and endogenous antioxidants. The responses suggest that,
in humans, these substances may be beneficial by reducing the deleterious effects of a dietary overload of cholesterol. 相似文献
10.
E. Gerasimova N. Perova I. Ozerova V. Polessky V. Metelskaya I. Sherbakova M. Levachev S. Kulakova Yu. Nikitin T. Astakhova 《Lipids》1991,26(4):261-265
Native Chukot Peninsula residents, in contrast to Muscovites, consume a diet rich in n−3 polyunsaturated fatty acids. This
dietary peculiarity is reflected in differences in plasma lipid and apolipoprotein contents. The Chukot residents have lower
contents of total cholesterol, triglyceride, LDL (low density lipoprotein) cholesterol and apolipoprotein B, but higher HDL
(high density lipoprotein) cholesterol levels than do Muscovites. The apolipoprotein A-I levels were identical in both groups.
A higher HDL cholesterol to apolipoprotein A-I ratio was determined in the coastline Chukot residents (0.52±0.01) than in
Muscovites (0.43±0.01; p<0.01). In contrast to Muscovites, the coastline Chukot residents also had higher n−3 and lower n−6
polyunsaturated fatty acid percentages in plasma and erythrocyte lipids, and lower phosphatidylcholine and higher sphingomyelin
or phosphatidylethanolamine levels in HDL2b and HDL3. The higher HDL cholesterol levels in the plasma of the coastline Chukot residents appears to reflect the higher cholesterol-scavenging
capacity of their HDL.
We conclude from this study that the regular consumption of dietary n−3 polyunsaturated fatty acids by the coastline Chukot
residents decreased LDL cholesterol transfer from plasma to peripheral cells, and enhanced cholesterol efflux from cellular
membranes toward HDL. 相似文献
11.
The incorporation of L-4,5-[3H]leucine into the ultracentrifugally separated apolipoproteins of very low, low, and high density lipoproteins (VLDL, LDL,
HDL) and into serum albumin was found three-to four-fold higher in nephrotic than in normal rats one hour after intravenous
injection. Incorporation of leucine into the circulating lipids was negligible. Increases of similar magnitude were obtained
in the incorporation of simultaneously injected 1,5[14C] citrate into the lipids of VLDL, LDL, and HDL of nephrotic rats. Of the citrate carbons incorporated into serum and liver
lipids, the proportion in cholesterol was higher in nephrotic rats when compared to normal rats. The incorporation of both
precursors into total proteins and lipids of the liver vs. the incorporation into the lipoproteins was relatively lower in
nephrotic than in control rats, indicating a preferential channeling into secretable products. The occurrence of enhanced
new lipid synthesis in nephrosis was corroborated by the finding of markedly enhanced synthesis of lipoprotein-borne fatty
acids and cholesterol from3H2O. These results point out that while leucine is not an efficient in vivo precursor of lipoprotein lipids in nephrosis, de
novo lipogenesis proceeds from other precursors. Similar trend of changes, though of smaller magnitude, was elicited in rats
after double plasmapheresis, 18 hr apart, when measured 3 hr after the second plasma withdrawal. This indicates that the loss
of circulating proteins either by direct removal or through kidney lesion stimulates the compensatory hepatic response involving
excessive lipoprotein synthesis. Time-course studies showed that peak incorporation of leucine and citrate into the protein
and lipid components of lipoproteins, respectively, as well as into serum albumin, occurred coincidentally 3 hr after the
second plasmapheresis, suggesting an interdependence of the enhanced protein and lipid synthesis. 相似文献
12.
Nicotine, a major component of cigarette smoke, plays an important role in the development of cardiovascular disease and lung
cancer in smokers. The effect of nicotine on lipoprotein metabolism was studied using rats as the experimental animal. There
was a significant increase in the total cholesterol, phospholipids, and triglycerides as well as the amount of lipids associated
with very low density lipoprotein (VLDL) and low density lipoprotein (LDL) in sera of nicotine-treated rats. The incorporation
of 3H labeled leucine into the apo B was found to be increased both in the medium and associated cells in the hepatocytes isolated
from nicotine-treated rats indicating an increased synthesis and secretion of the apo B containing lipoproteins. This was
further confirmed by the higher incorporation of 14C acetate into total and individual lipids of LDL and VLDL secreted into the medium as well as that associated with different
lipids in the cell layer. The activity of lipoprotein lipase in extrahepatic tissues and plasma lecithin cholesterol acyltransferase
activity were significantly lower in nicotine-treated rats. These results indicate that nicotine exerts hyperlipidemic effects
particularly by increasing the synthesis and secretion of triglyceride-rich lipoproteins. Since nicotine is one of the major
hazardous components present in cigarette smoke and tobacco, one can extrapolate that the deleterious effect exerted by nicotine
on rats extends to cigarette smokers and those who use other forms of tobacco. 相似文献
13.
Klaus G. Parhofer Thomas Demant Michael M. Ritter H. Christian Geiss Markus Donner Peter Schwandt 《Lipids》1999,34(4):325-335
Lipoprotein (a) [Lp(a)] is a low-density lipoprotein (LDL) particle with an additional apolipoprotein named apo(a). The concentration
of Lp(a) in plasma is determined to a large extent by the size of the apo(a) isoform. Because elevated Lp(a) concentrations
in plasma are associated with risk for premature coronary heart disease it is important to determine whether variations in
production or catabolism mediate differences in Lp(a) concentration. We determined metabolic parameters of Lp(a) in 17 patients
with heterozygous familial hypercholesterolemia or severe mixed hyperlipidemia by fitting a monoexponential function to the
rebound of Lp(a) plasma concentration following LDL-apheresis. In 8 of those 17 patients this was done twice following two
different aphereses. Although this approach allows one to estimate metabolic parameters without the use of a tracer, it requires
several major assumptions such as that apheresis itself does not change production or catabolism of Lp(a) and that Lp(a) metabolism
can be described by a single compartment. One apheresis decreased Lp(a) concentration by 59.1±8.3%. The fractional catabolic
rate (FCR) was 0.16±0.12 d−1 and production rate 6.27±5.26 mg·kg−1·d−1. However, observed (concentration before first apheresis) and predicted steady-state concentrations differed considerably
(more than 20%) in 9 of 17 patients, indicating that not all assumptions were fulfille in all patients. Production rate but
not FCR was correlated with Lp(a) plasma concentration (r
2=0.43. P=0.004) and molecular weight of apo(a) (r
2=0.48, P=0.011), which confirms radiotracer experiments showing that variations in Lp(a) plasma concentrations are due to differences
in production not catabolism. When parameters were estimated tiwce in a subgroup of eight patients, satisfactory reproducibility
was observed in six patients. Although parameters determined on two occasions correlated well, only FCR was concordant (intraclass
correiation coefficient). Thus, despite the limitations arising from the assumptions implicit to this method, metabolic parameters
of Lp(a) can be estimated from the rebound of plasma concentration following apheresis.
Parts of this study were presented at the meeting of the International Atherosclerosis Society, Paris, October 5–9, 1997. 相似文献
14.
Effect of chronic glucagon administration on lipoprotein composition in normally fed,fasted and cholesterol-fed rats 总被引:2,自引:0,他引:2
Catherine Guettet Najmuddin Rostaqui Denis Mathe Bernard Lecuyer Nicole Navarro Bernard Jacotot 《Lipids》1991,26(6):451-458
Male adult Wistar rats received daily (at 9 a.m. and 5 p.m.) 10 μg of zinc-protamine glucagon by subcutaneous injection for
8 days. Plasma cholesterol levels were decreased by 36% in fed rats, 33% in cholesterol-fed rats and by 55% in fasted rats.
Lipoproteins were separated into 22 fractions by ultracentrifugation using a density gradient. Glucagon administration decreased
the cholesterol content in all lipoproteins except low density lipoprotein (LDL1) (1.006–1.040) and very low density lipoprotein (VLDL) from cholesterol-fed rats. The main decrease (−57 to −81%) was observed
in 1.050–1.100 g/mL lipoproteins (LDL2 and HDL2), which contained a large amount of apo E, while HDL3 cholesterol was not affected. Triacylglycerol levels were decreased only in chylomicrons and VLDL (−70%) of fed and cholesterol-fed
rats, while plasma and lipoprotein triacylglycerol levels were not changed in fasted rats treated with glucagon. In normally
fed rats glucagon administration increased by 42% the fractional catabolic rate of [125I]HDL2 while the absolute catabolic rate appeared to be unchanged. Glucagon seems to be a potent hypolipidemic agent affecting mainly
the apo E-rich lipoproteins. Its chronic administration limits lipoprotein accumulation which occurs upon cholesterol feeding. 相似文献
15.
M. Hossein Nouri-Sorkhabi David R. Sullivan David C. Roberts Philip W. Kuchel 《Lipids》1994,29(3):183-188
31P nuclear magnetic resonance (NMR) spectroscopy was used to measure the rate of acyl transfer from phosphatidylcholine (lecithin,
PC) in whole plasma and in high density lipoprotein (HDL). Spectral deconvolution was used to resolve overlapping resonances
in the31P NMR spectra of the phospholipids. Mean values of the acyl group transfer rates from PC in plasma and HDL were 36 μmol L−1h−1 and 19 μmol L−1h−1, respectively. The reciprocal nature of the decrease in the spectral peak intensities of PC, compared to the increase in
the intensities of the lysolecithin (lysoPC) peaks, suggested a substrate/product relationship consistent with the action
of lecithin:cholesterol acyltransferase (LCAT), the enzyme responsible for the esterification of free cholesterol in plasma.
LCAT involvement was confirmed by measuring the cholesterol esterification rate based on the13C NMR spectra obtained on lipid extracts from plasma that had been incubated at 37°C. Within experimental error, the rate
of lysoPC formation in plasma was shown to be equal to that of cholesteryl ester formation. 相似文献
16.
During lipolysis of chylomicron triacylglycerol by lipoprotein lipase, arachidonic acid (AA) esters are hydrolyzed at a slower
rate than the predominant 16–18 carbon fatty acid esters. The further metabolism of the AA that is hereby enriched in the
chylomicron remnant acylglycerols has not been investigated. In the present study, we examined the low density lipoprotein
(LDL) dependent and independent metabolism of [14C]AA present in chylomicron remnants in the human hepatoma cell line Hep G2. Mesenteric duct cannulated rats were fed [14C]AA and [3H]cholesterol in corn oil, and the chyle obtained was injected intravenously into hepatectomized rats to form chylomicron
remnants labeled with [14C]AA in the triacylglycerol (TG) and with3H in the cholesteryl ester portion. The remnants were then incubated with Hep G2 cells. The uptake of [14C]AA within 2–4 h was similar to that of [3H]cholesteryl ester. After uptake into the cells, [14C]AA was preferentially incorporated into phospholipids, a high proportion being found in phosphatidylcholine, phosphatidylethanolamine
and phosphatidylinositol. [14C]AA and [3H]cholesteryl ester uptake were influenced to similar extents by factors unknown to regulate the LDL receptor and by an anti-LDL
receptor antibody. Addition of compactin thus increased the uptake of [14C]AA by 50% in 4 h and mevalonolactone decreased the uptake by 86%. Using an anti-LDL receptor antibody, 25.0% of [3H]cholesterol/cholesteryl ester and 37.7% of [14C]AA binding to the cells at 4°C were blocked. There was no lipolysis of [14C]TG or [14C]diacylglycerol by lipase secreted into the medium during incubations. The study shows that after the uptake of chylomicron
remnants by Hep G2 cells, which in part occursvia the LDL receptor, AA is liberated from the acylglycerols and is preferentially incorporated into phospholipids. 相似文献
17.
The influence of lipolytic mechanisms on the transfer of phospholipids and unesterified cholesterol from artificial emulsions,
serving as chylomicron models to other plasma lipoproteins, mainly high density lipoproteins (HDL) were testedin vivo. The emulsions labeled with radioactive lipids were injected into the bloodstream of rats (controls) and the results were
compared with those obtained from rats that had previously been treated with Triton WR 1339 or heparin. Plasma clearance and
the distribution of cholesteryl esters, phospholipids and unesterified cholesterol in the different plasma lipoprotein fractions
were then determined. Whereas virtually no cholesteryl esters were found in d>1.006 g/mL density fraction of the three experimental
groups, 2.8±1.3% of the injected phospholipids were in the 1.063–1.210 g/L density fraction of the Triton treated rats, and
12.6±5.4% of the heparin treated rats, as compared to 10.1±1.7% in controls. This indicates that lipolysis directly influences
phospholipid transfer to HDL. In contrast, free-cholesterol transfer to HDL, besides being less pronounced than phospholipid
transfer, was enhanced by Triton and diminished by heparin, indicating that lipolytic mechanisms were not important determinants
in this process.
This work is part of a Privatdozent Thesis by the corresponding author. 相似文献
18.
Anne Javouhey-Donzel Lucien Guenot Véronique Maupoil Luc Rochette Gérard Rocquelin 《Lipids》1993,28(7):651-655
Three groups of sixteen male rats each were fed semipurified diets containing 15% by weight of lipid for a period of 4 wk.
The diets contained the same amount of polyunsaturated fatty acids (PUFA) (20% of total fatty acids) and saturated fatty acids
(19% of total fatty acids). Dietary PUFA were represented exclusively by linoleic acid (18∶2 diet), or 10% linoleic acid and
10% linolenic acid (18∶3 diet), or 10% linoleic acid and 10% long-chain n−3 fatty acids (LCn−3 diet). The overall amount of
vitamin E was similar in the three diets,i.e, 140, 133 and 129 mg/kg diet, respectively. Following appropriate extraction, tocopherol levels in heart, liver, brain, adipose
tissue (AT) and plasma were measured by high-performance liquid chromatography. The level of vitamin E in the heart decreased
with n−3 PUFA diets, most markedly with LCn−3 PUFA. Liver and AT vitamin E contents also decreased with n−3 PUFA diets when
expressed as μg/mg total lipids and μg/mg phospholipids, respectively. Total plasma vitamin E was lower in rats fed the LCn−3
diet, but there was no significant difference when expressed as μg/mg total lipids. Brain vitamin E was not affected by the
various diets.In vitro cardiac lipid peroxidation was quantified by the thiobarbituric acid reactive substances (TBARS) test. Heart homogenates
were incubated at 37°C for 15 and 30 min in both the absence (uninduced) or presence (induced) of a free radical generating
system (1 mM xanthine, 0.1 IU per mL xanthine oxidase, 0.2 mM/0.4 mM Fe/ethylenediaminetetraacetic acid). TBARS release was
time-independent but significantly higher when LCn−3 fatty acids were fed to rats in either the uninduced or induced system.
The study demonstrated that n−3 PUFA diets can influence vitamin E status of rats even in short-term experiments and can change
the susceptibility of the heart toin vitro lipid peroxidation. 相似文献
19.
G. W. Meijer A. F. H. Stalenhoef P. N. M. Demacker M. J. T. M. Mol L. F. M. Van Zutphen A. C. Beynen 《Lipids》1992,27(6):474-477
In two inbred strains of rabbits with high or low response of plasma cholesterol to dietary cholesterol, low density lipoprotein
(LDL) apolipoprotein (apoLDL) kinetics were determined with the use of a heterologous tracer isolated from a Watanabe heritable
hyperlipidemic (WHHL) rabbit. On a diet without added cholesterol, the total clearance of apoLDL (which equals apoLDL production)
did not differ significantly between rabbits of both strains. After the feeding of a diet containing 0.1% cholesterol for
six weeks, plasma LDL cholesterol, plasma apoLDL and liver cholesterol concentrations rose significantly in the hyperresponsive
but not in the hyporesponsive rabbits. Cholesterol feeding depressed the total fractional catabolic rate (FCR) of apoLDL in
the hyper- but not in the hyporesponsive rabbits; this was attributed to a decrease of receptor-dependent FCR while receptor-independent
FCR was similar in the two strains. On the diet containing cholesterol, the receptor-mediated absolute catabolic rate (ACR)
of apoLDL did not differ between hyper- and hyporesponsive rabbits but receptor-independent ACR of apoLDL was higher in hyperresponders.
It is concluded that the higher plasma apoLDL levels in hyperresponsive rabbits fed the 0.1% cholesterol diet are caused by
a higher production of apoLDL and not by a lower flux of apoLDL through the receptor-mediated pathway. 相似文献
20.
Guinea pigs have varying plasma triglyceride concentrations ranging from 28 to 1392 mg/dl, with relatively uniform plasma
cholesterol and phospholipid levels. To understand why the animals exhibit such wide variations of plasma triglyceride concentrations,
we have explored the triglyceride hydrolyzing system by measuring tissue lipoprotein lipase activities and plasma activator
for the enzyme. Lipoprotein lipase activities of epididymal adipose tissue of these animals were 759±117 (mean±SE) n moles
FFA·min−1·g wet tissue−1, markedly low compared with those of rats. There were no relationships between plasma triglyceride concentrations and tissue
lipase activities. Plasma activator for lipoprotein lipase was lacking in this animal. Guinea pigs with ascorbic acid deficiency
for 2 weeks also showed marked variations of plasma triglyceride concentrations, without any changes in tissue lipoprotein
lipase activities. Low adipose tissue lipoprotein lipase activities with deficient plasma activator for the enzyme suggest
that the lipoprotein lipase-mediated triglyceride degradation could be impaired in this animal, and this may account for the
marked variation of plasma triglyceride concentrations. 相似文献