Human plasma trans-sialidase causes atherogenic modification of low density lipoprotein.

In earlier studies we have found that incubation of low density lipoprotein (LDL) with autologous blood plasma-derived serum leads to a loss of sialic acid from lipoprotein particles. In this study we demonstrated that sialic acid removed from LDL was transferred to glycoconjugates of lipoproteins, glycoproteins and sphingolipids of human serum. This showed that human serum contained the trans-sialidase activity. Gel-filtration chromatography of human blood serum demonstrated the presence of trans-sialidase activity in lipoprotein subfractions as well as in lipoprotein-deficient serum. Trans-sialidase (about 65 kDa) was isolated from lipoprotein-deficient serum using affinity chromatography carried out with Neu5Acalpha2-8Neu5Ac-sepharose FF-6. Optimal pH values for the trans-sialidase were 3.0, 5.0 and 7.0. Calcium and magnesium ions stimulated the enzyme activity at millimolar concentrations. Isolated enzyme can remove sialic acid from LDL, IDL, VLDL, and HDL particles (in decreasing rate order). Serum trans-sialidase transferred sialic acid from glycoconjugates of plasma proteins (fetuin, transferrin) and gangliosides (GM3, GD3, GM1, GD1a, GD1b). Sialylated glycoconjugates of human blood erythrocytes also served as substrate for serum trans-sialidase. We have found that sialic acid can also be removed from N- and O-linked glycans, sialylated Le(x) and Le(a), oligosialic acids, and sphingolipid carbohydrate chains. The rate of sialic acid release decreased in the following order: alpha2,6>alpha2,3>alpha2,8. Transferred molecule of sialic acid can form alpha2,6, alpha2,3 and to a lesser degree alpha2,8 linkage with galactose, N-acetyl-galactosamine or sialic acid of acceptors. The glycoconjugates of erythrocytes, lipoprotein particles, plasma proteins, neutral sphingolipids and gangliosides may serve as acceptors of transferred sialic acid. Trans-sialidase-treated native LDL becomes desialylated and then can induce cholesteryl ester accumulation in human aortic intimal smooth muscle cells. Thus, trans-sialidase may be involved in the early stages of atherogenesis characterized by foam cell formation.     

Human serum gangliosides in hypercholesterolemia, before and after extracorporeal elimination of LDL.

Total content, pattern and transport by lipoproteins of gangliosides have been studied in the sera of 10 patients with hypercholesterolemia and manifest cardiovascular disease. Half of the patients with hypercholesterolemia and 3 healthy controls were treated with heparin-induced extracorporeal LDL precipitation (HELP). In the sera of the untreated group total gangliosides and cholesterol were elevated about 2-fold. Ratios of normal ganglioside components were not altered and abnormal ganglioside species not detected. Treatment with HELP resulted in an almost selective removal of lipid-bound sialic acid carried on LDL. The re-increase of total serum gangliosides was strictly correlated to that of LDL-cholesterol and apolipoprotein B. Total gangliosides and ratios of individual components carried on single LDL- and HDL-particles were not altered by the HELP treatment. Our results indicate that gangliosides are excreted into the serum along with nascent apolipoprotein B-containing lipoproteins, which are of hepatic origin. In hypercholesterolemia excretion of gangliosides into the circulation is elevated and surplus of circulating gangliosides is bound to increased numbers of 'atherogenic' LDL. Biosynthesis of different ganglioside components, most probably by the liver, and total amount of gangliosides bound to lipoprotein particles seem not to be altered.     

Statin treatment increases the sialic acid content of LDL in hypercholesterolemic patients

Low density lipoprotein (LDL) with low sialic acid content has been reported to cause intracellular cholesterol accumulation, and therefore desialylation has been proposed to be an atherogenic modification of LDL. However, it is not known whether hypolipidemic treatment has any effect on LDL sialylation. Accordingly, we investigated the sialic acid/apolipoprotein (apo) B ratio of total LDL and its subfractions in 26 moderately hypercholesterolemic patients at baseline and after treatment with statins for 2-3 months. Cholesterol and triglyceride levels were reduced in all apo B-containing lipoproteins, including all LDL subfractions, while the sialic acid ratio was increased in total LDL and in all its subfractions. Cholesterol concentrations and sialic acid ratios were inversely correlated in light and dense LDL subfractions both before and during statin treatment, and the greater the decrease in cholesterol and apo B contents of dense LDL, the higher was the increase in its sialic acid ratio. Furthermore, the lower the baseline sialic acid ratio of dense LDL, the greater was the reduction in its lipid and apo B concentrations. In conclusion, inhibition of cholesterol synthesis by statin treatment increased sialic acid/apo B ratio in LDL proportionately to the decrease of LDL apo B and cholesterol.     

Modulation of the synthesis of apolipoproteins in rat hepatoma cells

The present study was designed to investigate whether plasma lipoproteins and albumin can affect the basal synthetic rate of apolipoproteins in differentiated rat hepatoma cells (Fao) incubated in serum-free medium. The synthesis of apolipoproteins was measured by the incorporation of [35S]methionine into medium lipoproteins isolated by density gradient ultracentrifugation. Under all the experimental conditions used, Fao cells synthesized almost exclusively apolipoprotein E. When cells were incubated in the presence of 5-10% rat plasma the synthesis of apolipoprotein E increased 2-3-fold; lipoprotein-deficient serum had a negligible effect. Fatty acid-poor bovine serum albumin (BSA), which had been found to reduce very-low-density lipoprotein secretion in isolated rat hepatocytes, did not modify the synthesis of apolipoprotein E. When Fao cells were incubated in medium containing rat plasma lipoprotein fractions, the synthesis of apolipoprotein E increased. The d less than 1.090 g/ml plasma lipoprotein fraction had the major stimulatory effect. Increased apolipoprotein E synthesis was observed when cells were incubated in the presence of lipids extracted from rat plasma lipoproteins. These results suggest that the intracellular accumulation of lipoprotein-lipids plays an important role in regulating apolipoprotein E synthesis in Fao cells.     

Beta-very low density lipoproteins in cholesterol-fed rabbits are of hepatic origin

When rabbits are fed a cholesterol-rich diet they accumulate beta-migrating very low density lipoprotein (beta-VLDL) in their plasma. beta-VLDL are cholesteryl ester-rich lipoproteins which contain apolipoproteins B and E. There are 2 forms of apolipoprotein B in beta-VLDL. About 90% of apolipoprotein B is present as a 320 000-dalton protein and the remainder is present as a 210 000-dalton protein. These apolipoproteins are tissue specific. Lipoproteins secreted by perfused rabbit livers contain only the 320 000-dalton apolipoprotein B while lipoproteins secreted by the intestine contain only the 210 000-dalton apolipoprotein B. The tissue specificity of apolipoprotein B shows that beta-VLDL is largely of hepatic origin and that only a small fraction is of intestinal origin. The composition of VLDL secreted from the livers of cholesterol-fed rabbits is similar to that of plasma beta-VLDL. Both are cholesteryl ester-rich, in contrast to plasma and perfusate VLDL from normal rabbits which are both triglyceride-rich. This indicates that the cholesteryl ester-rich hepatic VLDL is a direct precursor for plasma beta-VLDL.     

Influence of smoking, body fat distribution, and alcohol consumption on serum lipids, lipoproteins, and apolipoproteins in early postmenopausal women

The impact of smoking, alcohol consumption, obesity, and body fat distribution (measured either directly by dual photon absorptiometry as abdominal fat% (AF%) or as the waist-to-hip ratio (WTH] on serum lipids, lipoproteins, and apolipoproteins was investigated in 148 early postmenopausal women. All the women were healthy and none were taking medication known to influence the parameters studied. Smokers had significantly higher levels of triglycerides, low density lipoprotein cholesterol (LDL-C), and apolipoprotein B (P less than 0.05), and higher ratios of LDL-C/HDL-C and apolipoprotein B/A-I (P less than 0.01), but lower levels of high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (P less than 0.01). Moderate alcohol consumption was positively associated with HDL-C and apolipoprotein A-I (P less than 0.001). Body weight and body mass index (BMI) tended to be positively associated with an atherogenic lipoprotein and apolipoprotein profile. However, body fat distribution parameters (AF% and WTH) were stronger predictors of lipoproteins and apolipoproteins than were body weight and BMI, which did not seem to be independent predictors of lipoproteins and apolipoproteins. We conclude that cigarette smoking and a central fat distribution have a significant, independent, negative influence on lipids, lipoproteins, and apolipoproteins, whereas moderate alcohol consumption has a positive effect on these parameters in early postmenopausal women.     

Synaptic membrane complex carbohydrates in experimental hepatic encephalopathy

To evaluate further the status of synaptic plasma membranes (SPMs) in the brain in the syndrome of hepatic encephalopathy (HE) lipid- and protein-bound sialic acid and ganglioside and protein composition were investigated in SPMs from the brains of six rabbits with galactosamine-induced fulminant hepatic failure and five normal rabbits. HE was associated with no appreciable changes in the Chromatographic pattern of gangliosides or the concentration of protein-bound sialic acid, but the syndrome was associated with a 20% increase in lipid-bound sialic acid and, as assessed electrophoretically, an increase in the concentration of a protein with a molecular weight of about 70 kDa. Thus, changes in the composition of complex carbohydrates and protein in SPMs occur in a model of HE. The findings raise the possibility that nonhumoral factors, such as increased sialylation of glycolipids, contribute to the generation of abnormal neurotransmission in HE.     

Effect of desialylation of very low-density lipoproteins on their catabolism by lipoprotein lipase

Very low-density lipoproteins (VLDL) contain sialylated apolipoproteins (apo) (eg, apo CIII1-3) that inhibit apo CII activation of lipoprotein lipase (LPL) and also uptake of triglyceride (TG)-rich lipoproteins by the liver. Hypertriglyceridemic patients can have an excess of sialylated apo CIII (apo CIII1 or apo CIII2) in VLDL. These observations have prompted the notion that sialic acid in VLDL may impede LPL or receptor-mediated clearance of VLDL and thus result in hypertriglyceridemia. The aim of this study was to determine whether desialylation of VLDL altered their property as a substrate for LPL. VLDL isolated from five hypertriglyceridemic patients was desialylated with neuraminidase, labeled with a fluorescent probe, dansyl phosphatidylethanolamine and 600 micrograms of labeled VLDL TG were incubated with a constant amount of purified bovine LPL. The change in fluorescence against time was monitored on a recorder to yield curves representing continuous lipolysis of VLDL by LPL. Mean initial velocity of reaction (Vi) and extent of lipolysis measured as total increase in fluorescence over baseline at 30 minutes (F30/FO) were similar (Vi = 10.2 +/- 0.37 control v 10.2 +/- 0.42 u/min desialylated VLDL; F30/FO = 4.1 +/- 0.15, control v 4.1 +/- 0.07 desialylated VLDL; n = 5). Thus, sialic acid does not influence VLDL catabolism by LPL. Our study does not exclude a possible role of the sialic acid in receptor mediated uptake of remnants produced by initial catabolism of VLDL by LPL.     

Serum lipids and apolipoproteins in children with Type 1 (insulin-dependent) diabetes during the first two years of the disease

Summary Serum lipoproteins and apolipoproteins were studied at diagnosis and 6,12 and 24 months later in 30 consecutive children aged 3–15 years with newly detected Type 1 (insulin-dependent) diabetes mellitus (December 1982–October 1984) and in 44 healthy control children. Serum triglycerides at diagnosis were significantly higher than after 6–24 months and also higher than in the control group (p<0.001). At follow-up, triglycerides in the very low density lipoproteins and low density lipoproteins were restored to normal, while high density lipoprotein triglycerides remained high. Serum cholesterol at onset of diabetes was significantly higher than in the control children (p<0.01), mainly because of increased very low density lipoprotein cholesterol (p<0.001). Cholesterol in serum and in the serum lipoprotein fractions was similar to that in the control children at follow-up, except that high density lipoprotein cholesterol was higher in the diabetic children after 6 months. The concentrations of the serum apolipoproteins A-I, A-II and B were higher at onset of diabetes than in the control children (p<0.001, p<0.01, p<0.05 respectively), with a significantly increased ratio of apolipoprotein A-I to A-II in the diabetic children (p<0.001). The serum apolipoprotein concentrations were normalised during treatment. The ratio of apolipoprotein A-I to B did not differ from that in control children. On admission, there were strong positive correlations between HbA_1c and the concentrations of the very low density lipoproteins and the low density and high density lipoprotein triglycerides. There were also significantly positive correlations (p<0.01) between HbA_1c and apolipoprotein A-I and apolipoprotein B respectively. After treatment these correlations disappeared, except for a positive correlation with very low density lipoprotein triglycerides at 2 years. In conclusion, at diagnosis, when the diabetic children were in an insulin-deficient state, all apolipoproteins and serum lipoprotein fractions, except cholesterol in high density lipoproteins and low density lipoproteins were increased. During the first two years of treatment the concentrations of lipoproteins and apolipoproteins in serum are similar to those in healthy children.     

Abnormalities in lipoprotein metabolism in Gaucher type 1 disease

We have previously described an association between Gaucher type 1 disease and reduced levels of total, low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol. Plasma concentrations of apolipoprotein B and apolipoprotein AI were reduced in these subjects, while plasma apolipoprotein E (apoE), which can be synthesized and secreted by macrophages, was increased. To study the pathophysiologic basis for these changes in lipoprotein and apolipoprotein levels, we studied very low density lipoprotein (VLDL), LDL, and HDL metabolism in-depth in four subjects with Gaucher disease. Gel filtration of their plasma revealed that apoE was present in essentially a single population of lipoproteins in the large HDL range. In subject no. 4, studied presplenectomy and post-splenectomy, plasma apoE levels fell after surgery in association with a redistribution of apoE among the plasma lipoproteins to a pattern seen in normal subjects. Determination of the rates of secretion and catabolism of VLDL apoB and triglyceride were within normal limits. The reduced plasma levels of LDL and HDL cholesterol, and of both plasma apoB and apoAI, were associated with increased fractional catabolic rates of these apolipoproteins in LDL and HDL. These results indicate that the hypocholesterolemia present in subjects with Gaucher type 1 disease is associated with increased fractional catabolism of LDL and HDL. These findings, together with the evidence for alternations in plasma apoE metabolism in this disorder, suggest a role for the macrophage as the basis for these abnormalities.     

Characterization of plasma lipids and lipoproteins in patients with beta 2-glycoprotein I (apolipoprotein H) deficiency

The fasting plasma lipids, lipoproteins, and apolipoproteins were evaluated in 5 subjects with undetectable levels of the plasma protein beta 2-glycoprotein I (apolipoprotein H). Family studies confirmed an autosomal co-dominant inheritance pattern for the concentrations of apo H. The total lack of this protein is rare and less than 0.3% of clinic patients demonstrated levels undetectable by radial immunodiffusion. Plasma lipoprotein evaluation in these subjects with beta 2-glycoprotein I absence by analytical ultracentrifugation and compositional analysis demonstrated low concentrations of HDL2b and HDL3. More striking, however, was the lack of a consistent marked effect on the plasma lipoproteins as is found in other apolipoprotein deficiency states. We conclude that the lack of apolipoprotein H does not result in a significant perturbation of normal lipoprotein metabolism as reflected by analysis of fasting plasma lipoproteins. Further study is required to evaluate the role of this glycoprotein in the metabolism of triglyceride-rich lipoproteins.     

A year-long study of changes induced by thyroidectomy in the plasma lipid and lipoprotein spectrum in the European badger

Hypothyroidism is associated with hypercholesterolemia and increased risk for atherosclerotic disease. The European badger exhibits large seasonal changes in thyroid activity and the annual minimum of plasma thyroxine level in this species occurs at the same period of the year (i.e. late fall) as a pronounced hypercholesterolemia. We examined the plasma lipid and lipoprotein spectrum in a group of thyroidectomized male badgers every month for a year. Non-operated animals were used as controls. Our analyses included measurement of plasma lipid levels, density gradient ultracentrifugation of lipoproteins, electrophoresis of lipoproteins and apolipoproteins, and histological studies. Maximal differences between the two groups of animals were observed during spring, occurring concomitantly with the annual maximum of plasma thyroxine concentration in control badgers. Comparison with the latter animals revealed a permanent hypercholesterolemia and hyperphospholipidemia in thyroidectomized badgers, while their lipoprotein spectrum was characterized by the continual presence of elevated concentrations of cholesterol-rich lipoproteins of d congruent to 1.015 - 1.027 g/ml. The ratio of triglyceride/cholesteryl ester content in such lipoproteins remained constant throughout the year, resembling that noted in intact animals during late fall. Other features distinguishing the lipoprotein spectrum in thyroidectomized badgers were: (1) higher levels of lipoproteins with d 1.027 - 1.065 g/ml and d 1.065 - 1.100 g/ml, and (2) a cholesteryl ester enrichment of both these lipoprotein subclasses. The two groups of animals shared a heterogeneity of low density lipoprotein subfractions isolated on density gradients, together with the presence of apolipoproteins with molecular weights respectively typical of human apolipoproteins A-I and B throughout the low density range. Arterial walls and heart tissues from intact and thyroidectomized animals were free of atherosclerotic lesions at the end of the experimental period.     

The concept of apolipoprotein-defined lipoprotein families and its clinical significance

Classification of plasma lipoproteins on the basis of apolipoprotein (apo) composition recognizes two lipoprotein (Lp) classes, one of which is characterized by apoA-I and the other by apoB as major protein constituents. The former lipoprotein class consists of three major subclasses referred to (according to their apolipoprotein constituents) as Lp-A-I, Lp-A-I:A-II, and Lp-A-II, and the latter one of five subclasses called Lp-B, Lp-B:E, Lp-B:C, Lp-B:C:E, and Lp-A-II:B:C:D:E. As polydisperse systems of particles, the apoA-I-containing lipoproteins overlap in high-density segments and apoB-containing lipoproteins in low-density segments of the density gradient. Each subclass is characterized by a specific chemical composition and metabolic property. Normolipidemia and dyslipoproteinemias are characterized by quantitative rather than qualitative differences in the levels of apoA- and apoB-containing subclasses. Furthermore, apoA-containing subclasses seem to differ with respect to their relative antiatherogenic capacities, and apoB-containing subclasses regarding their relative atherogenic potentials. Whereas Lp-A-I may have a greater antiatherogenic capacity than other apoA-containing subclasses, the cholesterol-enriched Lp-B:C appears to be the most atherogenic subclass among apoB-containing lipoprotein families. The use of pharmacologic and/or dietary interventions to treat dyslipoproteinemias has already shown that these therapeutic modalities may affect selectively individual apolipoprotein-defined lipoproteins, and thus allow the selection of individualized treatments targeted at decreasing harmful and/or increasing beneficial lipoprotein subclasses.     

Changes in the levels and composition of lipoproteins and apolipoproteins of blood plasma in patients with ischemic heart disease after hemosorption

Prior to and following activated charcoal hemosorption, concentrations of lipids, apolipoproteins AI and B and lipid and protein composition in lipoprotein fractions isolated by ultracentrifugation were determined in the plasma from patients with coronary heart disease. The majority of the patients showed a parallel proportional decrease in plasma atherogenic parameters and all components of very low density lipoproteins and low density lipoproteins, triglycerides in particular. Antiatherogenic parameters, such as high density lipoprotein and apo-AI cholesterol, and all the components in high density lipoprotein subfractions were less reduced. In 19% of the patients, hemosorption failed to affect plasma lipids and apolipoproteins. The findings suggest that, in case of successful hemosorption, apoB-containing lipoproteins are chiefly eliminated as whole complexes from the plasma and that this procedure is most beneficial in hypertriglyceridemia.     

Metabolic effects of a biphasic oral contraceptive preparation containing ethinyloestradiol and desogestrel on serum lipoproteins and apolipoproteins

The effect of the administration of a biphasic oral contraceptive containing ethinyloestradiol and desogestrel on the distribution and composition of serum lipoproteins was studied in a group of 17 healthy female volunteers. The women were treated for a period of 6 months and compared with a control group of ten untreated volunteers. The serum lipoproteins were fractionated by density gradient ultracentrifugation into very low density lipoproteins (VLDL), low density lipoproteins (LDL), and into the high density lipoprotein (HDL) subfractions 2 and 3 (HDL2, HDL3). Lipids and apolipoproteins were assayed in the various fractions. No modification of either the lipid or apolipoprotein concentrations was observed in the control group. In the treated group, sex hormone-binding globulin (SHBG) and cortisol-binding globulin (CBG), and the serum content of cholesterol, triglycerides, HDL-cholesterol, apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II) increased significantly after 3 and 6 months. The cholesterol and apolipoprotein B (apo B) content of VLDL increased significantly after 3 and 6 months, but remained unchanged in LDL. High density lipoprotein subfraction 2 (HDL2)-cholesterol was significantly increased after 3 and 6 months but apo A-I only after 6 months. Since apo A-II did not change, the apo A-I/A-II ratio increased significantly after 6 months of treatment. In the HDL3 fraction, the apo A-I increase was significant after 3 and 6 months, while the increase of apo A-II was significant after 6 months. The apo A-I/A-II ratio remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Associations of abdominal adiposity, fasting insulin, sex hormone binding globulin, and estrone with lipids and lipoproteins in post-menopausal women

The associations of abdominal adiposity, fasting serum levels of insulin, and sex hormones with blood lipids, lipoproteins, and apolipoproteins A-I and B were studied cross-sectionally in 75 healthy, postmenopausal white women. In univariate analyses, abdominal adiposity (increased waist-to-hip girth ratio) and fasting insulin concentrations were negatively and significantly associated (P less than 0.05) with plasma high density lipoprotein cholesterol (r = -0.47 and -0.38, respectively) and apolipoprotein A-I (r = -0.37 and -0.36), and positively associated with log triglycerides (r = 0.54 and 0.33) and apolipoprotein B (r = 0.43 and 0.22). Sex hormone binding globulin was positively and significantly associated with high density lipoprotein cholesterol (r = 0.32) and negatively associated with log triglyceride (r = -0.45) and apolipoprotein B (r = -0.36). Estrone was positively and significantly associated with high density lipoprotein cholesterol (r = 0.27), apolipoprotein A-I (r = 0.23) and negatively associated with low density lipoprotein cholesterol (r = -0.24) and apolipoprotein B (r = -0.25). Total estradiol, free estradiol, free testosterone, and total testosterone were more weakly associated with the lipid measures. In multivariate analyses, abdominal adiposity remained significantly associated with high density lipoprotein cholesterol, log triglycerides, apolipoproteins A-I and B after adjustment for sex hormone binding globulin, estrone, and insulin concentrations. Insulin remained associated only with apolipoprotein A-I after adjustment for abdominal adiposity, estrone, and sex hormone binding globulin. Sex hormone binding globulin remained marginally associated with log triglyceride (P = 0.07) after adjustment for the remaining three factors. Estrone remained significantly associated with high density lipoprotein cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of different insulin regimens on plasma lipoprotein and apolipoprotein concentrations in patients with non-insulin-dependent diabetes mellitus

The effect of insulin treatment with 2 different insulin regimens on the plasma concentrations of lipoproteins and apolipoproteins A1 and B was studied in 10 patients with non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to oral hypoglycaemic agents. The investigation was performed as a randomized crossover study with treatment periods of 8 weeks. Insulin was given either as mainly intermediate acting insulin before breakfast and dinner (2-dose insulin) or as regular insulin preprandially with intermediate acting insulin at bedtime (4-dose insulin). A similar improvement in glycaemic control was obtained with both insulin regimens. On treatment with oral agents the patients were found to have higher total plasma triglycerides and lower plasma high density lipoprotein (HDL) cholesterol than a matched non-diabetic control group. Insulin treatment almost completely normalized these lipid disturbances by reducing mean total plasma triglycerides with 36% and increasing plasma HDL cholesterol with 20% on 2-dose and 17% on 4-dose. The triglyceride concentration in the very low density lipoprotein (VLDL) fraction was reduced. Mean plasma low density lipoprotein (LDL)-cholesterol was not affected by any treatment. There was an increase of similar magnitude in both HDL2 and HDL3 concentrations but only the change in the HDL3 subfraction was statistically significant. Mean plasma apolipoprotein A1 concentration increased with 9% (P less than 0.05) while there was no significant change in the plasma apolipoprotein B concentration. The changes in the plasma concentrations of lipoproteins and apolipoproteins A1 and B were almost identical on 2- and 4-dose insulin.(ABSTRACT TRUNCATED AT 250 WORDS)     

载脂蛋白A5对甘油三酯代谢的影响及其机制

载脂蛋白A5是载脂蛋白家族的新成员,它具有较强的表面排斥力和很强的脂质结合能力.在动物与人类研究中发现,它主要参与调节甘油三酯代谢,但两者之间的关系目前研究结果尚不一致.它可通过维持细胞内脂滴的形态、影响肝细胞极低密度脂蛋白-甘油三酯的产生、增加血浆富舍甘油三酯脂蛋白的清除及增加脂蛋白脂肪酶和肝酯酶的活性调节甘油三酯的代谢,但其具体机制仍有待进一步研究.     

Immunofluorescence studies of apolipoprotein B in intestinal mucosa. Absence in abetalipoproteinemia.

During fat absorption, active synthesis of cholesterol, phospholipids, and specific apolipoproteins are required for chylomicron formation and secretion. In the inherited disease abetalipoproteinema, chylomicrons cannot be made in response to fat feeding, and they as well as low and very low density lipoproteins are completely absent from plasma. The genetic defect in the disease is presumed to be an inability to synthesize apolipoprotein B, the apoprotein common to all the above lipoprotein classes, but such a defect has not been directly demonstrated. With peroral intestinal biopsies and immunofluorescence and intracellular localization of apolipoprotein B within jejunal epithelial cells of five normal subjects and have shown that its content increases markedly after fat feeding. In two patients with abetalipoproteinemia no apolipoprotein B was seen by immunofluorescence techniques in the jejunal mucosa in the fasting state or after a fatty meal. Intestinal synthesis of apolipoprotein B appears not to occur in abetalipoproteinemia.     

The role of cholesterol and phosphatidylcholine on very low density lipoprotein secretion from rat hepatocytes

The role of cholesterol and phosphatidylcholine on hepatic very low density lipoprotein secretion was investigated with rat hepatocytes. Hepatic very low density lipoprotein secretion (apo B, apo E, cholesterol, triglyceride, phosphatidylcholine) was decreased by the reduction of hepatic phosphatidylcholine content. However, cholesterol loading into hepatocytes did not affect hepatic very low density lipoprotein secretion. Hepatic apolipoprotein contents were constant and were not influenced by a change of hepatic cholesterol and phosphatidylcholine contents. These results suggest that lipids, which are constituents of lipoproteins, play different roles on hepatic very low density lipoprotein secretion.