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Biomedical subjects

Y Oschry

Publications and source records attributed to Y Oschry.

33 records · Page 2Linked to original sources
PubMed1985

Defective metabolism of hypertriglyceridemic low density lipoprotein in cultured human skin fibroblasts. Normalization with bezafibrate therapy.

The metabolism of hypertriglyceridemic low density lipoprotein (HTG-LDL) was investigated in upregulated cultured human skin fibroblasts. Low density lipoprotein (LDL) was isolated by zonal centrifugation from the plasma of seven HTG subjects, before and 2 wk after the initiation of bezafibrate (BZ) therapy. HTG-LDL is a cholesterol-poor, triglyceride-rich lipoprotein of smaller diameter than BZ-LDL or normal LDL (N-LDL). Binding, cell association, and proteolytic degradation of HTG-LDL were compared with that of BZ-LDL and N-LDL and were found to be significantly lower by a paired t test analysis (P less than 0.001). After 6 h preincubation with unlabeled HTG-LDL, the incorporation of [14C]acetate to sterols was significantly higher than with BZ-LDL or N-LDL (577 +/- 43.7; 330 +/- 41.5; 262 +/- 47, mean +/- SE, picomoles sterols per milligram cell protein per 2 h, respectively; P less than 0.001 by paired t test). To determine the effectiveness of HTG-LDL and BZ-LDL on the down-regulation of LDL receptor activity, up-regulated cells were incubated for 48 h with HTG-LDL and BZ-LDL. LDL receptor activity was significantly higher after preincubation with HTG-LDL compared with BZ-LDL, and the rates of sterol synthesis were similarly increased. These results demonstrate that HTG-LDL does not down-regulate the LDL receptor activity as efficiently as BZ-LDL and that its cholesterol content is not enough to adequately suppress cellular sterol synthesis. Significant correlation between LDL composition and cholesterol synthesis by cultured cells was found with all LDL preparations over a wide range of cholesteryl ester to protein ratio (0.8-2.2). This correlation indicates that the compositional and structural abnormalities of HTG-LDL, and especially the low cholesterol content of the lipoprotein, alter LDL metabolism and cellular cholesterol formation.

Bezafibrate↗
PubMed1985

Is hypertriglyceridemic very low density lipoprotein a precursor of normal low density lipoprotein?

The precursor-product relationship of very low density (VLDL) and low density lipoproteins (LDL) was studied. VLDL obtained from normal (NTG) and hypertriglyceridemic (HTG) subjects was fractionated by zonal ultracentrifugation and subjected to in vitro lipolysis. The individual subfractions and their isolated lipolysis products, as well as IDL and LDL, were rigorously characterized. A striking difference in the contribution of cholesteryl ester to VLDL is noted. In NTG subfractions, the cholesteryl ester to protein ratio increases with decreasing density (VLDL-I----VLDL-III). This is the expected result of triglyceride loss through lipolysis and cholesteryl ester gain through core-lipid transfer protein action. In HTG subfractions there is an abnormal enrichment of cholesteryl esters that is most marked in VLDL-I and nearly absent in VLDL-III. Thus, the trend of the cholesteryl ester to protein ratios is reversed, being highest in HTG-VLDL-I and lowest in VLDL-III. This is incompatible with the precursor-product relationship described by the VLDL----IDL----LDL cascade. In vitro lipolysis studies support the conclusion that not all HTG-VLDL can be metabolized to LDL. While all NTG subfractions yield products that are LDL-like in size, density, and composition, only HTG-VLDL-III, whose composition is most similar to normal, does so. HTG VLDL-I and VLDL-II products are large and light populations that are highly enriched in cholesteryl ester. We suggest that this abnormal enrichment of HTG-VLDL with cholesteryl ester results from the prolonged action of core-lipid transfer protein on the slowly metabolized VLDL mass. This excess cholesteryl ester load, unaffected by the process of VLDL catabolism, remains entrapped within the abnormal particle. Therefore, lipolysis yields an abnormal, cholesteryl ester-rich product that can never become LDL.

Adult↗
PubMed1984

Removal defect of very-low-density lipoproteins from diabetic rats.

The disappearance rate of triacyl[3H]glycerol carried on very-low-density lipoproteins (VLDL), isolated from diabetic rats and reinjected into normal recipient rats, was about twice as low as that of VLDL-triacyl[3H]glycerol from non-diabetic rats. The VLDL derived from diabetic rats was deficient in the apolipoprotein E component. These results indicate that the triacylglycerol removal defect in diabetes may be related to the quality of the protein carrier.

Animals↗
PubMed1984

Abnormalities in very low, low and high density lipoproteins in hypertriglyceridemia. Reversal toward normal with bezafibrate treatment.

The effects of triglyceridemia on plasma lipoproteins were investigated in 16 hypertriglyceridemic (HTG) subjects (222-2,500 mg/dl) before and after the initiation of bezafibrate therapy. Bezafibrate caused a mean reduction of 56% in plasma triglyceride and increased the levels of lipoprotein and hepatic triglyceride lipases by 260 and 213%, respectively. The natures of very low density lipoprotein (VLDL), isolated at plasma density and of low and high density lipoprotein (LDL and HDL), separated by zonal ultracentrifugation, were determined. HTG-LDL appears as multiple fractions whereas HTG-HDL is seen predominantly as HDL3. HTG-VLDL is relatively poor in apoproteins and triglycerides but enriched in free and esterified cholesterol. HTG-LDL (main fraction) is depleted of free and esterified cholesterol but enriched in apoprotein and triglyceride. It is also denser and smaller than normal. HTG-HDL3 is denser than N-HDL3 and demonstrates compositional abnormalities similar to those of HTG-LDL. With the reduction of the VLDL mass, all abnormalities revert towards normal. This is accompanied by an increase in LDL-apoprotein B and cholesterol levels, which indicates an increased conversion of VLDL to LDL. Significant correlations between plasma triglyceride and the degree of all abnormalities are shown. The data obtained during treatment corroborate these relationships. The observations support the concept that most abnormalities reflect the degree of triglyceridemia. We suggest that plasma core-lipid transfer protein(s) is an effector of the abnormal cholesteryl ester distribution. Its prolonged action on increasingly large and slowly metabolized VLDL populations would entail a correspondingly excessive transfer of cholesteryl ester to VLDL and of triglyceride to LDL and HDL. It is calculated that, in moderate HTG, LDL and HDL contain only 50% of the normal cholesterol load. It is suggested that cholesteryl ester redistribution in HTG might be important in regulating metabolic events.

Adult↗
PubMed1984

Intravascular metabolism of the cholesteryl ester moiety of rat plasma lipoproteins.

The intravascular metabolism of the cholesteryl ester moiety of rat plasma LDL, HDL1, and HDL2 was determined in intact male rats. Biosynthetically labeled lipoproteins were prepared by zonal ultracentrifugation from the plasma of rats injected with [3H]cholesterol. The lipoproteins were concentrated by vacuum ultrafiltration as other procedures were found to alter the biological properties of the lipoproteins. After injection of labeled LDL, [3H]cholesteryl esters remained with the injected lipoprotein and decayed from plasma with a t1/2 of 7-8 hours. [3H]Cholesteryl esters in HDL1 behaved similarly and decayed with a t1/2 of 10.5 hours. With HDL2, however, a different metabolic pattern was observed with intraplasma conversion of some [3H]cholesteryl ester HDL2 particles to HDL1. Since such conversion of HDL2 to HDL1 was not observed after in vitro incubations of rat plasma, this process seems to depend on metabolic events that occur in vivo. [3H]Cholesteryl esters disappeared from HDL2 with a t1/2 of 6-7 hours, while the esters that were transferred to HDL1 decayed with a t1/2 of 10-11 hours, similar to labeled cholesteryl esters injected with HDL1. The study demonstrated that the high apoE content of rat plasma HDL1 is not associated with rapid catabolism of the lipoprotein and that a major source of HDL1 in the rat is the intraplasma conversion of HDL2 particles to HDL1.

Animals↗
PubMed1984

Unusual dyslipoproteinemia in a patient with primary systemic amyloidosis and nephrotic syndrome. Role of excessive cholesterol synthesis.

We describe a patient with primary systemic amyloidosis, nephrotic syndrome and unusual dyslipoproteinemia. Levels of plasma cholesterol greater than 2,000 mg/dl and triglycerides greater than 3,000 mg/dl were observed. As much as 70% of the plasma cholesterol separated into abnormal very-low-density lipoprotein (VLDL) with cholesterol ester/triglyceride weight ratio of 0.7-1.0. Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) were also elevated, and high-density lipoprotein (HDL) was low. Both LDL and HDL were triglyceride rich. Neither IDL nor LDL was detected after in vitro lipolysis of VLDL triglycerides (95%); hence, IDL and LDL were most probably secreted directly from liver cells. Treatment by weekly plasma exchange was instituted, and the progression of the amyloidosis was slowed. Endogenous cholesterol synthesis, estimated from increments of plasma cholesterol after exchange, was greater than 2,000 mg/dl. We conclude that the unusual dyslipoproteinemia observed in this patient represents a special type of nephrotic syndrome with remarkably enhanced endogenous cholesterol production.

Amyloidosis↗
PubMed1983

Metabolic heterogeneity of post-lipolysis rat mesenteric lymph small chylomicrons produced in vitro.

The study was undertaken to investigate the metabolic rat of post-lipolysis mesenteric lymph small chylomicrons produced in vitro. Small chylomicrons doubly labeled with [3H]cholesterol (more than 70% in cholesteryl esters) and [14C]palmitate-labeled triglycerides were collected from rat mesenteric lymph during periods of fasting. Lipolysis was performed in vitro with lipoprotein lipase purified from bovine milk. More than 98% of the chylomicron-triglycerides could be hydrolyzed to fatty acids. Post-lipolysis chylomicrons were separated by zonal ultracentrifugation, characterized, and tested for biological behavior in intact rats. Following lipolysis the lipoproteins lost nearly all their triglycerides, apoA-I, and apoC, and were relatively enriched with cholesteryl esters, unesterified cholesterol, phospholipids, and apoB. Three preparations were tested for biological behavior: pooled (total) post-lipolysis chylomicrons (diameter approximately 250 A); particles at the ascending part of the zonal effluent (diameter approximately 300 A), and at the descending part (diameter approximately 200 A). After intravenous injection to intact rats, [3H]cholesteryl ester decay was very rapid with pooled lipoproteins and the 300-A preparation (t1/2 = 5-10 min). The 200-A preparation in contrast stayed in circulation much longer (t1/2 = 60-90 min). The study thus demonstrated metabolic heterogeneity of post-lipolysis small chylomicrons and indicated that some may form an LDL-like subpopulation with a plasma lifetime slower than "remnants" but faster than LDL.

Animals↗
PubMed1982

Preferential uptake of lipids by mycoplasma membranes from human plasma low-density lipoproteins.

The binding and transfer of low-density lipoprotein (LDL) constituents to mycoplasma membranes were examined. Mycoplasma capricolum was found to bind more 125I-labeled LDL than Acholeplasma laidlawii. Free and esterified cholesterol uptake was 3-4 times higher in M. capricolum than in A. laidlawii. Cholesterol transfer to the membranes of both organisms far exceeded the amounts of cholesterol expected according to LDL protein found associated with the membranes. Trypsin digestion of the membranes prior to incubation with LDL decreased the binding of LDL and the transfer of free cholesterol to M. capricolum membranes but did not affect these processes with A. laidlawii membranes. These findings suggest the existence of protease-sensitive receptors on M. capricolum cell surface responsible for tighter contact with LDL. Analysis of LDL after incubation with large amounts of M. capricolum membranes revealed a loss of 60% of the lipoprotein-free cholesterol, 25.9% of the esterified cholesterol, and 20.7% of phospholipids without appreciable loss of protein. Rate zonal ultracentrifugation showed that the LDL separated as a single symmetrical peak, denser than the control. Electron microscopy showed that the lipoprotein particles retained their spherical shape but became about 10% smaller in diameter. These observations lead us to conclude that both free and esterified cholesterols are transferable from LDL to the membranes by a simple exchange process which does not involve prolonged contact or fusion of the particle with the membrane and does not result in degradation of the lipoprotein particle. We propose that similar mechanisms of free and esterified cholesterol transfer may also operate in vivo and contribute to the process of cholesterol exit from the plasma.

Acholeplasma laidlawii↗
PubMed1982

Abnormal high density lipoproteins of abetalipoproteinemia: relevance to normal HDL metabolism.

We investigated high density lipoprotein (HDL) subfractions in abetalipoproteinemia (ABL) using rate zonal ultracentrifugation. In ABL, HDL2 is the major subfraction, 65% of total mass compared to less than 10% in normal subjects with similar HDL levels. HDL2 and HDL3 in ABL (n = 3) are larger and lighter than in normals (n = 3), with mean diameters of 136 +/- 19 A and 100 +/- 12 A, respectively (as compared to 113 +/- 12 A and 86 +/- 11 A), and contained more apoprotein E. ABL-HDL2 and HDL3 particles contain 2- to 2.5-fold more cholesteryl ester molecules than normals. ABL-HDL can be modified towards normal HDL by allowing VLDL triglycerides to exchange for ABL-HDL cholesteryl esters, followed by addition of lipoprotein lipase and hydrolysis of the triglycerides. In addition, ABL plasma contains a previously undescribed small and spherical (61 +/- 8 A) protein-rich (63% by weight) HDL fraction, which we call ABL-HDL4. Our data suggest that absence of cholesteryl ester transfer to triglyceride-rich lipoprotein in ABL causes accumulation of abnormally large cholesteryl ester-rich particles.

Abetalipoproteinemia↗
PubMed1982

Rat plasma lipoproteins: re-evaluation of a lipoprotein system in an animal devoid of cholesteryl ester transfer activity.

Plasma lipoproteins from male rats were isolated by rate zonal centrifugation. Four lipoproteins were identified: VLDL, LDL, HDL1, and HDL2. LDL, HLD1, and some HDL2 distributed within the salt density interval of 1.006-1.085 g/ml, while HDL2 was found in the 1.063-1.21 g/ml interval. HDL3 was not identified in the rat. Rat VLDL is poor in cholesteryl esters (1.5-3.0% of total mass) and nearly lacks the smaller and denser particle subpopulation which is predominant in humans. Rat LDL, containing a relatively large amount of triglyceride (20.2% of total mass) and a small amount of cholesteryl ester (27.5%), could be isolated free of apoproteins other than apoB. HDL1 is a cholesteryl ester-rich lipoprotein that occupies a density interval overlapping both LDL and HDL2. ApoE is the major protein constituent of HDL1; apoA-I, A-IV, and C are also present. Apo-A-I-rich HDL2 is the only human-like HDL subpopulation found in rats. Lipoproteins from fasted and non-fasted rats were essentially similar. Arachidonic acid contributed 56.7% and 72.3% of total cholesteryl ester fatty acids in HDL1 and HDL2, respectively, but only 7.9% and 27.3% in VLDL and LDL, respectively. Palmitic, palmitoleic, and oleic acids were the major cholesteryl ester fatty acids in VLDL and LDL. In vitro incubation of biosynthetically labeled HDL2 cholesteryl ester with rat plasma demonstrated minimal transfer of the labeled cholesteryl ester to VLDL and LDL. These results indicate biological immiscibility of HDL cholesteryl esters with those of lower density lipoproteins. The finding of cholesteryl ester-poor VLDL and LDL and the presence of HDL as larger and less dense subpopulations is compatible with the absence of cholesteryl ester transfer activity in an animal with pronounced LCAT activity.

Animals↗
PubMed1981

Fat associated with adipose lipase. The newly synthesized fraction that is the preferred substrate for lipolysis.

The incorporation of fatty acids by adipocyte fat cake was observed. The newly formed lipid was not extracted by petroleum either but remained in the lipase-containing residue. It was the first lipid to be hydrolyzed when the lipase was activated by exposure to the aqueous phase. The data presented indicate that the lipid fraction of the fat layer residue is the active compartment of cell acylglycerol and demonstrate that the compartmentation of acylglycerols into metabolic pools involves a physical separation between them.

Adipose Tissue↗
PubMed1980

Lipolytic activity in adipocyte cell fractions.

Adipocytes release only negligible amounts of free fatty acids unless stimulated, but reveal considerable lipolytic activity when homogenized. Epinephrine treatment of the cells caused only a 20-40% increase in the activity of infranatants of homogenates while raising the activity associated with the fat layer up to 10-fold. Full activity (i.e. that of intact-activated cells) could be revealed by epinephrine treatment of the homogenate as well as by sonication of the fat layer in buffer. The combination of both treatments did not yield higher activities. The fat cake contains the bulk of the potential activities which are only realized when dispersed in the aqueous phase by sonication, or upon hormone activation of the whole homogenate. Increase in activity could also be obtained by removal of most of the lipid from the fat layer by extraction with petroleum ether. Re-introduction of extracted lipid inhibited lipolysis. The active enzyme could be separated by flotation at 1.12 specific gravity. The data suggest that the lack of activity in the intact non-stimulated cell may be due to the lack of availability of the aqueous phase to the enzyme.

Adipose Tissue↗
PubMedDate not supplied

Effect of weight loss in moderate obesity on plasma lipoprotein and apolipoprotein levels and on high density lipoprotein composition.

Plasma lipids, lipoprotein and apolipoprotein levels were determined in seven women and seven men with moderate obesity before, during 7 weeks of continuous weight loss (10.4% to 9.6% of body weight, 1000 kCal/day diet), and after 3 months at a stable, reduced weight. Plasma triglyceride levels decreased by 30.4% in men and by 39.4% in women (p less than 0.0001) after 1 week of caloric restriction and remained at this level throughout the study period. The plasma cholesterol decreased by 19.0% in men (p less than 0.001) and by 10.9% in women (p less than 0.01) in the period of active weight loss, but returned to prediet values after stabilization at a leaner body mass. Similar changes were observed in LDL cholesterol levels. No change in high density lipoprotein (HDL) cholesterol levels occurred during active weight reduction, but after 3 months at a reduced weight, a significant increase in HDL cholesterol was evident, and the ratio of HDL cholesterol to plasma cholesterol increased over prediet values (p less than 0.001), women). Separation of HDL subpopulations by zonal ultracentrifugation before and after weight reduction revealed that HDL2 increased slightly in men and decreased slightly in women. In both genders, HDL3 tended to decrease after weight reduction. Plasma levels of apolipoprotein A-I decreased during active weight loss, but this was significant only in women (p less than 0.05). After 3 months of reduced weight, plasma apo A-I increased to prediet levels. No significant changes in plasma apo A-II or apo E were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Plasma triglyceride determines structure-composition in low and high density lipoproteins.

Because the association of hypertriglyceridemia and premature atherosclerosis is not due to the direct effects of the triglyceride molecule itself, we studied the effects of increased plasma triglyceride-rich lipoproteins on the composition and structure of low density lipoprotein (LDL) and high density lipoprotein (HDL). We found profound changes in the core and surface domains of both lipoproteins with increasing triglyceridemia. Core cholesterol esters were progressively depleted and replaced by triglyceride molecules. Highly significant negative correlations were found between cholesterol ester/protein ratios (r = -0.64 for LDL and -0.58 for HDL (p less than 0.001); positive correlations were found for triglyceride/protein ratios (r = 0.62 for LDL and 0.58 for HDL) and for triglyceride/cholesterol ester ratios (r = 0.70 for LDL and 0.83 for HDL) when these variables were assayed as a function of plasma triglyceride concentrations. With severe hypertriglyceridemia, triglyceride/cholesterol ester ratios of more than 1.0 were consistently observed (normal, less than 0.02). This leads to an underestimation of LDL and HDL levels when cholesterol alone is measured. At the surface, LDL and HDL were depleted of phospholipid and free cholesterol, with a relative enrichment of protein. These changes can be explained on the basis of high levels of plasma triglyceride-rich lipoproteins serving as acceptors for cholesterol esters and other constituents from LDL and HDL. Concomitantly, triglycerides are transferred to LDL and HDL. These transfer processes are likely to be mediated by the activity of lipid transfer proteins present in human plasma.

Blood Proteins↗