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Protein composition was determined in mesenteric lymph chylomicrons from fat-fed rats. Among the proteins of intermediate molecular weight, apoproteins A-I and the arginine-rich apoprotein accounted for 31% and 4% of the total protein mass, respectively. Apoprotein B and apoprotein A-IV each accounted for about 10% and proteins of low molecular wei...
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Context 1
... antiserum did not react with apoA-I prepared from plasma HDL or from chylomicrons, nor with ARP prepared from plasma VLDL (Fig. 4). The identification of this chylo- micron protein as apoA-IV was supported by amino acid analysis ( Table 2). Because of its low content of tyrosine as compared with that of the other chylomi- cron apoproteins (21, 23) the value for absorbance at 280 nm underestimates its contribution to the pro- tein mass. ...
Citations
... TG-to-cholesterol mass ratio and primarily consist of apolipoprotein (Apo) B-48 and A-1. 16 These particles range from 75 to 3,000 nm in diameter, depending on the dietary lipid mass. 17 After interaction with high-density lipoprotein (HDL), the nascent CM becomes mature and acquires ApoC and ApoE on its surface. ...
... Among men and women over the age of 55 years, the incidence increased from 8.1% and 5.8% to 16.7% and 12.2%, respectively. In the cross-sectional study included in the CCHS, men with a previous ischemic stroke versus controls had nonfasting TG levels of 2. 16 44 Similar results were reported in 2011 when the CCHS reached a 33-year follow-up. 45 Moreover, increasing cholesterol levels were not associated with the risk of ischemic stroke except in men with cholesterol levels >9.00 mmol/L versus <5.00 mmol/L, with a HR of 4.40 (95% CI, 1.90 to 10.60). ...
Hypertriglyceridemia is caused by defects in triglyceride metabolism and generally manifests as abnormally high plasma triglyceride levels. Although the role of hypertriglyceridemia may not draw as much attention as that of plasma cholesterol in stroke, plasma triglycerides, especially nonfasting triglycerides, are thought to be correlated with the risk of ischemic stroke. Hypertriglyceridemia may increase the risk of ischemic stroke by promoting atherosclerosis and thrombosis and increasing blood viscosity. Moreover, hypertriglyceridemia may have some protective effects in patients who have already suffered a stroke via unclear mechanisms. Therefore, further studies are needed to elucidate the role of hypertriglyceridemia in the development and prognosis of ischemic stroke.
... ApoA-I synthesis and secretion in the lymph increase with lipid absorption by the intestine [102]. The protein is a major component of mesenteric lymph chylomicrons in rats, accounting for about one-third of total protein mass, with apoB accounting for about 10% [133]. In intestinal lymph, apoA-I accounts for 15-35 wt% of total chylomicron protein with apoB and apoA-IV accounting for 10% each, while the contribution of apoCs prevails at 42-50% [51,98]. ...
... Following secretion, most of chylomicron apoA-I is transferred to HDL during peripheral lipoprotein catabolism [132]. Similar transfers occur when chylomicrons are incubated in the presence of plasma in vitro [133,134]. While a majority of TGRL-derived apoA-I is transferred to large, lipid-rich spherical HDL, a small part of the protein associates with small, protein-rich pre-beta HDL [86,115]. ...
The failure of high-density lipoprotein (HDL)-raising agents to reduce cardiovascular disease (CVD) together with recent findings of increased cardiovascular mortality in subjects with extremely high HDL-cholesterol levels provide new opportunities to revisit our view of HDL. The concept of HDL function developed to explain these contradictory findings has recently been expanded by a role played by HDL in the lipolysis of triglyceride-rich lipoproteins (TGRLs) by lipoprotein lipase. According to the reverse remnant-cholesterol transport (RRT) hypothesis, HDL critically contributes to TGRL lipolysis via acquirement of surface lipids, including free cholesterol, released from TGRL. Ensuing cholesterol transport to the liver with excretion into the bile may reduce cholesterol influx in the arterial wall by accelerating removal from circulation of atherogenic, cholesterol-rich TGRL remnants. Such novel function of HDL opens wide therapeutic applications to reduce CVD in statin-treated patients, which primarily involve activation of cholesterol flux upon lipolysis.
... Lipid metabolism irregularities are linked to decreased nutrient absorption, upregulation of glycolysis, and TCA cycle activation in TEDDY IA subjects Intestine-to-blood lipid and vitamin transport are facilitated by lipoprotein particles known as chylomicrons [19]. A key chylomicron transmembrane protein, apolipoprotein A1 (APOA1), was identified in our analysis as a central model element (Fig. 5). ...
Background
The Environmental Determinants of Diabetes in the Young (TEDDY) is a prospective birth cohort designed to study type 1 diabetes (T1D) by following children with high genetic risk. An integrative multi-omics approach was used to evaluate islet autoimmunity etiology, identify disease biomarkers, and understand progression over time.
Results
We identify a multi-omics signature that was predictive of islet autoimmunity (IA) as early as 1 year before seroconversion. At this time, abnormalities in lipid metabolism, decreased capacity for nutrient absorption, and intracellular ROS accumulation are detected in children progressing towards IA. Additionally, extracellular matrix remodeling, inflammation, cytotoxicity, angiogenesis, and increased activity of antigen-presenting cells are observed, which may contribute to beta cell destruction. Our results indicate that altered molecular homeostasis is present in IA-developing children months before the actual detection of islet autoantibodies, which opens an interesting window of opportunity for therapeutic intervention.
Conclusions
The approach employed herein for assessment of the TEDDY cohort showcases the utilization of multi-omics data for the modeling of complex, multifactorial diseases, like T1D.
... Apolipoprotein (apo) B is the only protein contained in LDL 12 and can be purified with high purity and yield simply by gradient centrifugation. 13 We attempted to reconstitute/synthesize apoB-containing lipoparticles as hydrophobic/amphiphilic compound delivery vehicles. The reconstituted apoB lipoparticle (rABL) may be an ideal carrier for transporting hydrophobic and amphiphilic compounds. ...
... LDL was purified from human serum using potassium bromide (KBr) density gradient ultracentrifugation as described in a previous study. 13 LDL was delipidated by an ice-cold methanol/ether mixture, followed by thorough mixing. The protein samples were dried in a fume hood to remove any organic solvent residual. ...
To develop a drug delivery system (DDS), it is critical to address challenging tasks such as the delivery of hydrophobic and amphiphilic compounds, cell uptake, and the metabolic fate of the drug delivery carrier. Low-density lipoprotein (LDL) has been acknowledged as the human serum transporter of natively abundant lipoparticles such as cholesterol, triacylglycerides, and lipids. Apolipoprotein B (apo B) is the only protein contained in LDL, and possesses a binding moiety for the LDL receptor that can be internalized and degraded naturally by the cell. Therefore, synthetic/reconstituting apoB lipoparticle (rABL) could be an excellent delivery carrier for hydrophobic or amphiphilic materials. Here, we synthesized rABL in vitro, using full-length apoB through a five-step solvent exchange method, and addressed its potential as a DDS. Our rABL exhibited good biocompatibility when evaluated with cytotoxicity and cell metabolic response assays, and was stable during storage in phosphate-buffered saline at 4°C for several months. Furthermore, hydrophobic super-paramagnetic iron oxide nanoparticles (SPIONPs) and the anti-cancer drug M4N (tetra-O-methyl nordihydroguaiaretic acid), used as an imaging enhancer and lipophilic drug model, respectively, were incorporated into the rABL, leading to the formation of SPIONPs- and M4N- containing rABL (SPIO@rABL and M4N@rABL, respectively). Fourier transform infrared spectroscopy suggested that rABL has a similar composition to that of LDL, and successfully incorporated SPIONPs or M4N. SPIO@rABL presented significant hepatic contrast enhancement in T2-weighted magnetic resonance imaging in BALB/c mice, suggesting its potential application as a medical imaging contrast agent. M4N@rABL could reduce the viability of the cancer cell line A549. Interestingly, we developed solution-phase high-resolution transmission electron microscopy to observe both LDL and SPIO@rABL in the liquid state. In summary, our LDL-based DDS, rABL, has significant potential as a novel DDS for hydrophobic and amphiphilic materials, with good cell internalization properties and metabolicity.
... Statistically signifi cant differences in the average percentage composition of apolipoproteins from individual animals throughout the 8 h time course were not found (data not shown). Interestingly, the apolipoprotein patterns in mouse chylomicrons appeared similar to those isolated from nonhuman primates ( 21 ) and rats ( 13 ), with the following order of abundance: ApoC > ApoA-IV > ApoA-I > ApoB. ...
The hypothesis tested in this study was that cholesterol esterification by ACAT2 would increase cholesterol absorption efficiency by providing cholesteryl ester (CE) for incorporation into chylomicrons. The assumption was that absorption would be proportional to Acat2 gene dosage. Male ACAT2⁺/⁺, ACAT2⁺/⁻, and ACAT2⁻/⁻ mice were fed a diet containing 20% of energy as palm oil with 0.2% (w/w) cholesterol. Cholesterol absorption efficiency was measured by fecal dual-isotope and thoracic lymph duct cannulation (TLDC) methods using [³H]sitosterol and [¹⁴C]cholesterol tracers. Excellent agreement among individual mice was found for cholesterol absorption measured by both techniques. Cholesterol absorption efficiency in ACAT2⁻/⁻ mice was 16% compared with 46-47% in ACAT2⁺/⁺ and ACAT2⁺/⁻ mice. Chylomicrons from ACAT2⁺/⁺ and ACAT2⁺/⁻ mice carried ∼80% of total sterol mass as CE, whereas ACAT2⁻/⁻ chylomicrons carried >90% of sterol mass in the unesterified form. The total percentage of chylomicron mass as CE was reduced from 12% in the presence of ACAT2 to ∼1% in ACAT2⁻/⁻ mice. Altogether, the data demonstrate that ACAT2 increases cholesterol absorption efficiency by providing CE for chylomicron transport, but one copy of the Acat2 gene, providing ∼50% of ACAT2 mRNA and enzyme activity, was as effective as two copies in promoting cholesterol absorption.
... very low density lipoprotein (VLDL) assembliert und sezerniert. Diese tragen das Apolipoprotein B 100 und erhalten im Austausch mit HDL, ApoE und -C12 . Die VLDL werden wie die Chylomikronen auch mittels der LPL am Endothel, insbesondere im Fett-und Muskelgewebe, abgebaut. ...
... In fact, high concentrations of remnant-like (VLDL), and their remnants, in the blood circulation. Nascent chylomicrons, synthesized by enterocytes, have a high TG-to-cholesterol mass ratio, and consist primarily of apolipoprotein (apo) B-48 and apoA- 10,11) . After acquiring apoC-and apoE, chylomicrons bind to lipoprotein lipase (LPL), which induces lipolysis of TG in chylomicrons. ...
To characterize lipid profiles conveniently in the fasting period to detect postprandial hyperlipidemic subjects, we measured the concentrations of lipids, including remnant lipoproteins and apoB-48, before and after loading the test meal in 24 normolipidemic subjects.
We examined remnant-like particle-cholesterol and -triglyceride (RLP-C, RLP-TG) by the immune adsorption method, RemL-C by the newly developed homogeneous method, and apoB-48 by chemiluminescence enzyme immunoassay.
After loading, TG, RemL-C, RLP-C, RLP-TG, and apoB-48 concentrations were elevated. Twenty subjects had only a slight elevation of TG (low TG group) after loading, while 4 subjects showed apparent increase of TG (more than 150 mg/dL, high TG group). In the fasting period, the high TG group had significantly higher serum concentrations of TG and RemL-C than the low TG group. Although not significant, RLP-C, RLP-TG and apoB-48 concentrations in the high TG group were also higher than in the low TG group. After loading, serum concentrations of TG, RemL-C, RLP-C, RLP-TG, and apoB-48 increased significantly more in the high TG group than in the low TG group.
In conclusion, TG, RemL-C, RLP-C, RLP-TG, and apoB-48 concentrations in the fasting period may be suitable for detecting postprandial hyperlipidemic subjects.
... This has led to a considerable interest in CETP inhibitors as drugs to elevate HDL cholesterol levels. Administration of chemical inhibitors of CETP to rabbits (Imaizumi et al., 1978a,b) and humans (Sigurdsson et al., 1976 ) has resulted in significant elevations in HDL-cholesterol levels (Okamoto et al., 2000; Brousseau et al., 2004). The impact of CETP inhibitors on the development of atherosclerotic plaque is less clear (Okamoto et al., 2000; Huang et al., 2002; Shih et al., 2000). ...
Lipoproteins play a central role in transporting hydrophobic molecules through the bloodstream and between specific tissues. Lipoprotein molecules have a distinctive electrical charge and changes in electrostatic properties directly affect the metabolism of the lipoprotein. Lipoprotein charge controls interfacial interactions and determines the ability of the lipoprotein to interact with intravascular enzymes and cell surface proteins. Uniquely charged constituents of the lipoprotein thereby control the metabolism of lipoproteins by creating a regulatory system wherein the electrostatic properties of plasma lipoproteins determine the fate of intravascular lipids.
... The amount of apoA-I associated with VLDL was increased markedly by the HFD in both APOE3/3 and APOE4/4 mice (Fig. 1C) (12, 13). ApoA-I associates with chylomicrons (22)(23)(24). The increase in VLDL apoA-I levels in the plasma of fasted mice on the HFD results from a large increase in chylomicron remnant particles produced by this diet. ...
Withdrawing growth factors or serum from endothelial cells leads to the activation of effector caspases 3 and 7, resulting in apoptotic cell death. HDL protects against caspase induction through sphingosine-1-phosphate (S1P) receptors. This anti-caspase activity of HDL is antagonized by VLDL from apolipoprotein E4 (apoE4) (genotype, APOE4/4; apolipoprotein, apoE) targeted replacement (TR) mice, but not by VLDL from TR APOE3/3 mice, and requires the binding of apoE4-VLDL to an LDL receptor family member. In the absence of HDL, apoE4-VLDL and apoE3-VLDL from TR mice have limited antiapoptotic activity. In contrast, we show here that a high-fat/high-cholesterol/cholate diet (HFD) radically alters this biological activity of VLDL. On HFD, both apoE3-VLDL and apoE4-VLDL (HFD VLDL) inhibit caspase 3/7 activation initiated by serum withdrawal. This activity of HFD VLDL is independent of an LDL receptor family member but requires the activation of S1P(3) receptors, as shown by the ability of pharmacological block of S1P receptors by VPC 23019 and by small interfering RNA-mediated downregulation of S1P(3) receptors to inhibit HFD VLDL anticaspase activity.
... (cholesterol + cholesterol ester) content as 3.5% of total CM mass (Bhattacharya & Redgrave, 1981; Y.-G. Niu & R. D. Evans, results not shown), and CM apo-B content as 0.1% of total CM mass (Imaizumi et al. 1978;Bhattacharya & Redgrave, 1981), the difference between VLDL and CM uptake was even greater -about 4-fold (Fig. 2B). ...
Very-low-density lipoprotein (VLDL) and chylomicrons (CMs) transport triacylglycerol (TAG) to peripheral tissues. Lipoprotein-TAG may gain access to target cells by lipoprotein lipase (LPL) hydrolysis or via receptor-mediated uptake; the principal routes of entry of VLDL and CM into heart are unknown, and different routes of entry may result in different metabolic fates. To examine this, isolated working rat hearts were perfused with rat VLDL and CMs, dual-labelled with [3H]TAG and [14C]cholesterol. Uptake and utilization of CM-TAG were significantly greater than VLDL-TAG, but both were decreased significantly (more than halved) by tetrahydrolipstatin (THL, an inhibitor of lipoprotein lipase). By contrast, uptake of VLDL-cholesterol was much higher than CM-cholesterol (P < 0.01), and suramin (a lipoprotein receptor antagonist) decreased cholesterol uptake of both forms. CM-TAG oxidation rate was more than 4-fold higher than VLDL-TAG oxidation. However, suramin decreased TAG oxidation from both VLDL and CM without affecting TAG uptake or total utilization, suggesting that the TAG gaining access through receptor-mediated pathways is preferentially 'channelled' towards oxidation. Most (79%) CM-TAG was oxidized whilst the proportion of VLDL-TAG oxidized was only about half (49%). In the presence of suramin, there was a significant increase in esterification (incorporation of assimilated [3H]TAG into myocardial tissue [3H]lipids, mainly TAG) of assimilated TAG from both VLDL and CMs, again suggesting that receptor-mediated TAG uptake is directed towards oxidation rather than esterification. The importance of this relatively small pool of TAG is indicated by the fact that cardiac mechanical function declined markedly when lipoprotein receptors were inhibited. These results suggest that CMs, most fatty acids of which gain access into cardiomyocytes through LPL-mediated hydrolysis, are the major supplier of TAG for hearts to oxidize; however, the metabolic fate of VLDL was split evenly between oxidation and deposition as myocardial tissue lipid. Most importantly, VLDL may play a regulatory role in heart lipid metabolism through a lipoprotein receptor-mediated mechanism.
