Artificial Emulsion Research Articles

Uptake by macrophages of triacylglycerol-rich artificial emulsion particles co-incubated with native or with modified LDL is scavenger receptor-dependent

Uptake by macrophages of triacylglycerol-rich artificial emulsion particles co-incubated with native or with modified LDL is scavenger receptor-dependent

Uptake by macrophages of triacylglycerol-rich artificial emulsion particles co-incubated with native or modified LDL is a lipoprotein lipase-dependent process

Uptake by macrophages of triacylglycerol-rich artificial emulsion particles co-incubated with native or modified LDL is a lipoprotein lipase-dependent process

Uptake by macrophages of triacylglycerol-rich artificial emulsion particles co-incubated with native LDL is a clathrin-dependent process

Uptake by macrophages of triacylglycerol-rich artificial emulsion particles co-incubated with native LDL is a clathrin-dependent process

Mild oxidation of LDL by macrophages increases the uptake of triacylglycerol-rich artificial emulsion particles co-incubated with native LDL

Mild oxidation of LDL by macrophages increases the uptake of triacylglycerol-rich artificial emulsion particles co-incubated with native LDL

Differential inhibition of endocytosis of the triacylglycerol-rich artificial emulsion particles by macrophages

Differential inhibition of endocytosis of the triacylglycerol-rich artificial emulsion particles by macrophages

Macrophages take up triacylglycerol-rich artificial emulsion particles co-incubated with native or modified LDL by an actin-dependent mechanism

Macrophages take up triacylglycerol-rich artificial emulsion particles co-incubated with native or modified LDL by an actin-dependent mechanism

Metabolism of an artificial emulsion resembling chylomicrons in patients with multiple myeloma

Multiple myeloma, as other neoplastic diseases, is accompanied by alterations in lipid metabolism. The metabolism of chylomicrons is unexplored in this condition, dispite the importance of these lipoproteins for the energy body supply. Chylomicron metabolism in the bloodstream consists of lipolysis by lipoprotein lipase and uptake of remnants by the liver. Triglyceride-rich emulsions can mimic chylomicron metabolism in man and are a useful tool to evaluate this metabolic pathway. A double-labeled chylomicron-resembling emulsion was injected into 20 patients with multiple myeloma and 30 normolipidemic healthy subjects. The plasma kinetic curves of the emulsion 3H-triglyceride and 14C-cholesteryl ester were determined in plasma samples collected over 60 minutes. The fractional clearance rate (FCR) of triglycerides in multiple myeloma was not changed compared to controls. However, FCR of cholesteryl esters was smaller in multiple myeloma (0.025±0.003 and 0.061±0.010 min −1, respectively). These results indicate that chylomicron lipolysis is not affected in multiple myeloma, whereas remnant removal is diminished.

Metabolism of artificial chylomicrons emulsion on sedentary women after physical training program

Metabolism of artificial chylomicrons emulsion on sedentary women after physical training program

Macrophage uptake of triacylglycerol-rich artificial emulsion particles resembling chylomicrons is influenced by native and modified low density lipoprotein

Macrophage uptake of triacylglycerol-rich artificial emulsion particles resembling chylomicrons is influenced by native and modified low density lipoprotein

Drug effects on the metabolism of artificial triglyceride-rich emulsion particles resembling chylomicrons

Drug effects on the metabolism of artificial triglyceride-rich emulsion particles resembling chylomicrons

Smoking increases the lipolysis rate of an i.v. infused artificial TG-rich emulsion simulating chylomicrons

Smoking increases the lipolysis rate of an i.v. infused artificial TG-rich emulsion simulating chylomicrons

Chylomicron metabolism in experimental cirrhosis and cholestasis.

Recently it has been demonstrated that artificial emulsions made of lecithin, cholesterol, cholesteryl-oleate and triolein simulate the metabolism of the natural chylomicra. Artificial-chylomicron delipidation and remnant disappearance from plasma were investigated in rats with carbon tetrachloride-induced hepatic cirrhosis or with cholestasis due to bile-duct ligation. Artificial chylomicra were labelled simultaneously with glyceryl tri [9, 10 (N)-3H] oleate and cholesteryl [1-14C] oleate and injected intra-arterially. Simultaneous chylomicron delipidation and remnant removal by the liver were calculated from the plasma radioactivity decay curves: that of glyceryl tri [9, 10 (N)-3H] oleate signifying the combined delipidation and particle-removal processes, whereas that of cholesteryl [1-14C] oleate representing the particle disappearance rate from plasma. Particle delipidation was increased in cirrhosis and decreased in cholestasis, implying faster and slower lipolysis rates respectively. On the other hand, the remnant removal rate by the liver slowed down in both experimental pathologies.

Abnormal activation of lipoprotein lipase by non-equilibrating apoC-II: further evidence for the presence of non-equilibrating pools of apolipoproteins C-II and C-III in plasma lipoproteins

Using artificial triglyceride emulsions, we have demonstrated the presence of non-equilibrating pools of apolipoproteins C-II and C-III in human plasma lipoproteins. As the concentrations of acceptor triglycerides were increased, a greater fraction of both apoC-II and apoC-III shifted away from the native plasma lipoproteins to the artificial lipid emulsions. All of the apoC-II and apoC-III in very low density and high density lipoproteins (VLDL and HDL), however, could not be removed from native plasma lipoproteins. The percent of total plasma apoC-II and apoC-III that could be recovered in the VLDL and HDL density fractions varied when plasma from different individuals was used. When plasma samples from normotriglyceridemic subjects were used, HDL was the primary donor of apoCs. The percent of total plasma apoCs associated with HDL decreased from 60% to 25% for apoC-II and from 65% to 15% for apoC-III. When plasma samples from hypertriglyceridemic subjects were incubated with artificial lipid emulsions, VLDL was the primary donor of apoCs. HDL from hypertriglyceridemic subjects only accounted for 5-10% of total fasting plasma apoCs and did not contribute significantly to the final apoC contents of the artificial triglyceride emulsions. To evaluate the significance of the depletion of exchangeable apoCs from plasma HDL, we also examined the ability of control and apoC-depleted HDL to serve as activator for bovine milk lipoprotein lipase (LPL) in vitro. When HDL depleted of exchangeable apoCs were used as the source of plasma apolipoproteins for the activation of LPL in vitro, only 5-10% of the maximal activity obtained with native HDL was demonstrated. In fact, in the presence of comparable concentrations of HDL apoC-II, activation of LPL was the least with HDL which lacked exchangeable apoCs. Our data thus indicated that the presence of exchangeable apoC-II on HDL is necessary for the activation of LPL in vitro. This finding is consistent with our data that suggest that HDL from hypertriglyceridemic subjects do not stimulate LPL as well as HDL from normolipidemic subjects.

脂質分子集合体間の平衡とそれらのミクロな表面環境に関する界面化学的研究

Various lipid molecular assemblies, monolayer, bilayer, emulsion particle, hexagonal II phase and micellar particle, are in dynamic equilibrium in an animal body. Monolayer-bilayer equilibrium of a mixture of phospholipid and neutral lipid is influenced by the phase state of bilayer and molecular interaction of lipids. Neutral lipids, such as triglyceride, cholesterylester, ubiqinone-10 and α-tocopherol acetate form an emulsion structure with phosphatidylcholine (PC). Stable emulsion particles (neutral lipid core covered with PC monolayer) are in equilibrium with liposome particles (PC bilayers). This kind of equilibrium is important in catabolism of triglyceride-rich lipoprotein particles and artificial emulsion particles, Intralipid, in the plasma. Some other neutral lipids, such as diglyceride, menaquinone-4 and α-tocopherol induce a formation of intra-and inter-bilayer particles in PC bilayer, and finally transform it to hexagonal II phase. This type of neutral lipids has been implicated in several cellular processes : vesiculation, fusion, endocytosis and exocytosis etc. More hydrophilic lipid, such as cholate, or protein with amphiphatic helix, such as apoA-1, strongly interact with PC bilayer and transform it to micellar particles ; mixed disk micellar or high density lipoprotein particles. Phospholipid bilayer, therefore, converts into various nonbilayer structures by interaction with neutral lipid and protein in an animal body.

Effects of triton WR 1339 and heparin on the transfer of surface lipids from triglyceride‐rich emulsions to high density lipoproteins in rats

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 tested in 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 greater than 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.

Isolation of pure LpB from human serum.

Low density lipoproteins (LDL), even after isolation from a narrow density cut and after several washes by preparative ultracentrifugation, are contaminated by 3-5% non-apoB proteins. Incubation of these LDL with artificial triglyceride-rich lipid emulsions (TGRP) removed all contaminating apoC and also, under certain conditions, apoA proteins. TGRP treatment did not, however, change the lipid composition and the flotation behavior of LDL. Residual apoE and albumin, amounting up to 0.5% of the apoB mass, were resistant to removal by TGRP treatment as well as by heparin-Sepharose column chromatography. ApoE and albumin could only be removed by immunoabsorption.

Competition between chylomicrons and their remnants for plasma removal: a study with artificial emulsion models of chylomicrons

In previous studies, protein-free emulsions of defined lipid composition were shown capable of simulating either the metabolism of chylomicrons (chylomicron-like emulsion) or their remnants (remnant-like emulsion), depending on the content of free, unesterified cholesterol. To validate further the assumption that remnant-like and chylomicron-like emulsion have metabolic pathways in common with their natural counterparts, studies of competition for plasma removal were undertaken: the remnant-like emulsion labeled with [ 3H]triolein was injected sequentially twice in the carotid arteries of rats to compare the clearance of remnant-like emulsion of the second injection with the first (control). Prior to the second injection, a large bolus of the chylomicron-like emulsion or rat lymph chylomicron was injected, to check the hypothesis that remnant generated from chylomicron-like emulsion or natural chylomicrons could compete with and displace remnant-like emulsion particles from their tissue receptor sites. Experiments were also performed in rats treated with Triton WR-1339, to block the generation of remnants. Results showed that remnants derived from either natural chylomicrons or chylomicron-like emulsion both strongly competed with the remnant-like emulsion. In contrast, when transformation of remnants was prevented by Triton, the undegraded particles of chylomicron-like emulsion or natural chylomicron were unable to compete with or displace remnant-like emulsion from its sites of removal from the plasma. In agreement with plasma clearance data, the hepatic uptake of the remnant-like emulsion was inhibited by the surplus dose of natural chylomicrons. In contrast, the spleen uptake was unaffected by it.

Expression of a monoclonal antibody-defined aminoterminal epitope of human apoC-I on native and reconstituted lipoproteins.

Nine distinct mouse monoclonal antibodies were produced in two fusions using holo-human very low density lipoprotein (VLDL) as antigen. On immunoblotting first with human VLDL and then with isolated human apoC-I, seven of the antibodies, representing three isotypes, manifested specificity for apoC-I. Two antibodies were directed against apoB. To assess whether the seven anti-apoC-I antibodies were directed against the same or distinctively different epitopes, cross-competition assays were performed wherein 125I-labeled monoclonal antibodies were made to compete with unlabeled antibodies for occupancy on immobilized VLDL-associated apoC-I. All antibodies cross-competed to varying extents implying that they were directed against closely spaced epitopes, but based on these experiments three different epitopes were defined. On immunoblotting with CNBr fragments, all of the epitopes were assigned to the CNBr I fragment of human apoC-I (amino acids 1-38) suggesting that the NH2-terminal region of apoC-I is more immunogenic in mice than other parts of the molecule when apoC-I is associated with VLDL. A competitive solid-phase radioimmunoassay (RIA) was developed employing one of the anti-apoC-I antibodies (A3-4). VLDL was adsorbed to plastic microtiter wells, and a limiting amount of the antibody was reacted with the adsorbed VLDL. The amount of monoclonal antibody that bound to the immobilized VLDL-apoC-I was determined with a 125I-labeled goat anti-mouse IgG antibody. The addition of competitor apoC-I complexed with lipids resulted in reduced binding of the anti-apoC-I antibody to the immobilized VLDL-apoC-I. Competitor complexes consisted of an artificial lipid emulsion (Intralipid) incubated with apoC-I at phospholipid/apoC-I ratios of 1:1 to 60:1 (w/w). As the lipid/protein ratios were increased, the competitive displacement curves produced by the complexes become progressively steeper, while isolated lipid-free apoC-I produced curves with very shallow slopes, suggesting that a conformation-dependent epitope was being probed. Other apoproteins (C-II, C-III, A-I, A-II, and E) whether lipid-free or complexed with lipids did not compete. Fractionation of the 30:1 apoC-I-Intralipid complex by gel permeation chromatography suggested that apoC-I bound to phospholipids was the most effective competitor. This was confirmed by testing of apoC-I-DMPC complexes, which yielded curves that paralleled those produced by apoC-I-Intralipid.(ABSTRACT TRUNCATED AT 400 WORDS)

Metabolism of protein-free lipid emulsion models of chylomicrons in rats.

Emulsions were prepared by ultrasonication of mixtures of triolein, cholesteryl oleate, phosphatidylcholine and cholesterol in aqueous dispersions, then purified by ultracentrifugation. After injection into rats, the metabolism of the artificial, protein-free emulsions was comparable to the metabolism of chylomicrons collected from rat intestinal lymph during the absorption of fat. Like chylomicrons, the emulsion triacylglycerol was removed from the plasma more quickly than emulsion cholesteryl ester. Also like chylomicrons, much more emulsion cholesteryl ester than triacylglycerol appeared in the liver 10 min after injection, and only trace amounts appeared in the spleen. Because the artificial emulsions gained apolipoproteins when incubated with plasma, their metabolism was probably facilitated by the recipient rat plasma apolipoproteins and so, in rats made apolipoprotein-deficient by treatment with estrogen, the removal of emulsions from the plasma was slowed. Removal was also slowed in hyperlipidemic rats fed a high-fat, high-cholesterol diet to expand the plasma pools of the triacylglycerol-rich lipoproteins and remnants. The results indicate that the metabolism of lymph chylomicrons can be modeled by artificial, protein-free lipid emulsions not only in the initial partial hydrolysis by lipoprotein lipase, but also in the delivery of a remnant-like particle to the liver.

Role of lipid transfers in the formation of a subpopulation of small high density lipoproteins.

The effect of lipid transfers on the structure and composition of high density lipoproteins (HDL) has been studied in vitro in incubations that contained the lipoprotein-free fraction of human plasma as a source of lipid transfer protein. These incubations did not contain lecithin:cholesterol acyltransferase activity and were not supplemented with lipoprotein lipase. Incubations were performed at 37 degrees C for 6 hr in both the presence and absence of either added very low density lipoproteins (VLDL) or the artificial triglyceride emulsion, Intralipid. Incubation in the absence of added VLDL or Intralipid had little or no effect on the HDL. By contrast, incubation in the presence of either VLDL or Intralipid resulted in marked changes in the HDL. The effect of incubation with VLDL was qualitatively similar to that of Intralipid; both resulted in obvious transfers of lipid and changes in the density, particle size, and composition of HDL. Incubation of the plasma fraction of density 1.006-1.21 g/ml, total HDL, or HDL3 with either VLDL or Intralipid resulted in the following: 1) a depletion of the cholesteryl ester and free cholesterol content and an increase in the triglyceride content of both HDL2 and HDL3; 2) a decrease in density and an increase in particle size of the HDL3 to form a population of HDL2-like particles; and 3) the formation of a discrete population of very small lipoproteins with a density greater than that of the parent HDL3. The newly formed lipoproteins had a mean particle radius of 3.7-3.8 nm and consisted mainly of protein, predominantly apolipoprotein A-I and phospholipid.