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The Biochemical Journal Feb 1991Hepatic apolipoprotein (apo) B-100 isolated from human plasma is known to contain N-linked oligosaccharides of high-mannose-type and complex-type structures. Sequencing...
Hepatic apolipoprotein (apo) B-100 isolated from human plasma is known to contain N-linked oligosaccharides of high-mannose-type and complex-type structures. Sequencing data have revealed that apo B-48 of small-intestinal origin, which represents about 48% of apo B-100 polypeptide from the N-terminus, possesses six potential sites for N-linked oligosaccharides, of which five are likely to be glycosylated. The characterization of the carbohydrate moiety of apo B-48 is the focus of this study. Apo B-48 was labelled with L-[35S]methionine and D-[3H]glucosamine in organ culture of human small-intestinal explants. N-Glycanase treatment resulted in loss of radioactivity from D-[3H]glucosamine-labelled but not L-[35S]methionine-labelled apo B-48 secreted into the medium, and caused no distinct change in mobility of apo B-48 upon electrophoresis on 5% polyacrylamide gel. Analysis of monosaccharide content revealed the presence of 16.8, 17.8, 13.4, 3.4, 2.4 and 2.3 residues of N-acetylglucosamine, mannose, galactose, fucose, xylose and N-acetylgalactosamine respectively. Small-intestinal apo B-48 from human lymph chylomicrons bound to [14C]concanavalin A, and the binding could be inhibited with methyl alpha-D-mannoside. In addition, wheat-germ, peanut, Limulus, soya-bean and Ulex lectins bound apo B-48 specifically. To characterize the carbohydrate moiety further, N-linked oligosaccharides were released by N-Glycanase treatment and reduced with NaB3H4. Labelled oligosaccharides were separated on a concanavalin A-Sepharose column. The majority (78%) were biantennary complex-type structures, 16% were high-mannose type and 6% (not retained by the column) most probably represented higher-branched oligosaccharides. These results suggest the presence of one high-mannose-type and four biantennary complex-type oligosaccharides, as well as probable O-linked sugars in apo B-48. By the use of h.p.l.c., exoglycosidase treatments and ion-exchange chromatography, a mixture of high-mannose-type species with predominant Man8GlcNAc2 as well as monosialylated, desialylated and fucosylated forms of complex-type oligosaccharides were detected.
Topics: Apolipoprotein B-48; Apolipoproteins B; Carbohydrate Sequence; Chromatography, Affinity; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Humans; Jejunum; Methionine; Molecular Sequence Data; Muscle, Smooth; Oligosaccharides; Organ Culture Techniques; Sulfur Radioisotopes
PubMed: 2001228
DOI: 10.1042/bj2740159 -
Proceedings of the National Academy of... Mar 1993The concentration of triglyceride-rich lipoproteins containing apolipoprotein (apo) B-48 (chylomicrons) and apo B-100 (very low density lipoproteins) was measured in...
Relationships between the responses of triglyceride-rich lipoproteins in blood plasma containing apolipoproteins B-48 and B-100 to a fat-containing meal in normolipidemic humans.
The concentration of triglyceride-rich lipoproteins containing apolipoprotein (apo) B-48 (chylomicrons) and apo B-100 (very low density lipoproteins) was measured in blood plasma of healthy young men after an ordinary meal containing one-third of daily energy and fat. Plasma obtained in the postabsorptive state and at intervals up to 12 hr after the meal was subjected to immunoaffinity chromatography against a monoclonal antibody to apo B-100 that does not bind apo B-48 and a minor fraction of apo B-100 rich in apo E. Measurements of the concentrations of components of the total and unbound triglyceride-rich lipoproteins separated from plasma by ultracentrifugation showed that about 80% of the increase in lipoprotein particle number was in very low density lipoproteins containing apo B-100 and only 20% was in chylomicrons containing apo B-48 that carry dietary fat from the intestine. The maximal increments and the average concentrations of apo B-48 and B-100 during the 12 hr were highly correlated (r2 = 0.80), suggesting that preferential clearance of chylomicron triglycerides by lipoprotein lipase leads to accumulation of hepatogenous very low density lipoproteins during the alimentary period. The composition of the bulk of very low density lipoproteins that were bound to the monoclonal antibody changed little and these particles contained about 90% of the cholesterol and most of the apo E that accumulated in triglyceride-rich lipoproteins. The predominant accumulation of very low density lipoprotein rather than chylomicron particles after ingestion of ordinary meals is relevant to the potential atherogenicity of postprandial lipoproteins.
Topics: Adult; Animals; Apolipoprotein B-100; Apolipoprotein B-48; Apolipoproteins B; Apolipoproteins E; Cholesterol; Dietary Fats; Humans; Lipoproteins; Male; Mice; Triglycerides
PubMed: 8446630
DOI: 10.1073/pnas.90.5.2069 -
Nutrients Jun 2023We investigated the utilization of apolipoprotein B (ApoB), an independent risk factor for cardiovascular disease, and developed and validated a translational equation...
We investigated the utilization of apolipoprotein B (ApoB), an independent risk factor for cardiovascular disease, and developed and validated a translational equation for calculating low-density lipoprotein cholesterol (LDL-C) in the Korean population visiting local clinics and hospitals. Among a total of 469,520 data sets of the lipid profile panel (total cholesterol, triglycerides, and high-density lipoprotein cholesterols), 142,932 lipid test sets with data on LDL-C and/or ApoB were used for statistical analysis. Using linear regression analysis, we created ApoB percentile value-derived LDL-C equations in a creating set and validated them with previously reported equations (a total of 11 equations) in comparison to directly measured LDL-C using two independent validating sets. Among all lipid test sets, the simultaneously measured ApoB test only accounted for 2.0%, indicating its underutilization in Korea. The ApoB-derived equations, which were derived in this study and previous studies, showed an overall agreement of ≥94.3% for NCEP ATP III criteria. However, the accuracy of the equations varied among data sets of populations. Future studies are needed to validate translational equations for ApoB and LDL-C in different populations to clarify the clinical implications of these equations.
Topics: Humans; Cholesterol, LDL; Apolipoproteins B; Risk Factors; Cholesterol, HDL; Triglycerides; Hospitals; Republic of Korea; Apolipoprotein B-100
PubMed: 37375689
DOI: 10.3390/nu15122786 -
Journal of Lipid Research Dec 1984
Comparative Study Review
Topics: Animals; Apolipoprotein B-100; Apolipoproteins B; Humans; Hyperlipoproteinemia Type II; Lipoproteins, LDL; Lipoproteins, VLDL; Liver; Receptors, LDL
PubMed: 6397562
DOI: No ID Found -
The Journal of Clinical Endocrinology... Nov 2015Familial hypobetalipoproteinemia (FHBL) is a codominant disorder of lipoprotein metabolism characterized by decreased plasma concentrations of low-density lipoprotein...
CONTEXT
Familial hypobetalipoproteinemia (FHBL) is a codominant disorder of lipoprotein metabolism characterized by decreased plasma concentrations of low-density lipoprotein (LDL)-cholesterol and apolipoprotein B (apoB).
OBJECTIVE
The objective was to examine the effect of heterozygous APOB L343V FHBL on postprandial triglyceride-rich lipoprotein (TRL) and fasting lipoprotein metabolism.
METHODS
Plasma incremental area under the curve apoB-48 and apoB-48 kinetics were determined after ingestion of a standardized oral fat load using compartmental modeling. Very low-density lipoprotein (VLDL)-, intermediate-density lipoprotein (IDL)-, and LDL-apoB kinetics were determined in the fasting state using stable isotope methods and compartmental modeling.
RESULTS
The postprandial incremental area under the curve (0-10 h) in FHBL subjects (n = 3) was lower for large TRL-triglyceride (-77%; P < .0001), small TRL-cholesterol (-83%; P < .001), small TRL-triglyceride (-88%; P < .001), and for plasma triglyceride (-70%; P < .01) and apoB (-63%; P < .0001) compared with controls. Compartmental analysis showed that apoB-48 production was lower (-91%; P < .05) compared with controls. VLDL-apoB concentrations in FHBL subjects (n = 2) were lower by more than 75% compared with healthy, normolipidemic control subjects (P < .01). The VLDL-apoB fractional catabolic rate (FCR) was more than 5-fold higher in the FHBL subjects (P = .07). ApoB production rates and IDL- and LDL-apoB FCRs were not different between FHBL subjects and controls.
CONCLUSIONS
We conclude that when compared to controls, APOB L343V FHBL heterozygotes show lower TRL production with normal postprandial TRL particle clearance. In contrast, VLDL-apoB production was normal, whereas the FCR was higher in heterozygotes compared with lean control subjects. These mechanisms account for the marked hypolipidemic state observed in these FHBL subjects.
Topics: Adult; Amino Acid Substitution; Apolipoprotein B-48; Apolipoproteins B; Diet, High-Fat; Down-Regulation; Female; Heterozygote; Humans; Hypobetalipoproteinemia, Familial, Apolipoprotein B; Lipoproteins; Lipoproteins, IDL; Lipoproteins, VLDL; Male; Meals; Middle Aged; Models, Biological; Mutation; Postprandial Period; Triglycerides
PubMed: 26323024
DOI: 10.1210/jc.2015-2731 -
The Journal of Clinical Investigation Mar 2022Genetic variants at the SORT1 locus in humans, which cause increased SORT1 expression in the liver, are significantly associated with reduced plasma levels of LDL...
Genetic variants at the SORT1 locus in humans, which cause increased SORT1 expression in the liver, are significantly associated with reduced plasma levels of LDL cholesterol and apolipoprotein B (apoB). However, the role of hepatic sortilin remains controversial, as genetic deletion of sortilin in mice has resulted in variable and conflicting effects on apoB secretion. Here, we found that Sort1-KO mice on a chow diet and several Sort1-deficient hepatocyte lines displayed no difference in apoB secretion. When these models were challenged with high-fat diet or ER stress, the loss of Sort1 expression resulted in a significant increase in apoB-100 secretion. Sort1-overexpression studies yielded reciprocal results. Importantly, carriers of SORT1 variant with diabetes had larger decreases in plasma apoB, TG, and VLDL and LDL particle number as compared with people without diabetes with the same variants. We conclude that, under basal nonstressed conditions, loss of sortilin has little effect on hepatocyte apoB secretion, whereas, in the setting of lipid loading or ER stress, sortilin deficiency leads to increased apoB secretion. These results are consistent with the directionality of effect in human genetics studies and suggest that, under stress conditions, hepatic sortilin directs apoB toward lysosomal degradation rather than secretion, potentially serving as a quality control step in the apoB secretion pathway in hepatocytes.
Topics: Adaptor Proteins, Vesicular Transport; Animals; Apolipoprotein B-100; Apolipoproteins B; Hepatocytes; Humans; Lipoproteins, VLDL; Liver; Mice; Triglycerides
PubMed: 35113816
DOI: 10.1172/JCI144334 -
Molecular Biology of the Cell Feb 2022Apolipoprotein B (ApoB) is the primary component of atherogenic lipoproteins, which transport serum fats and cholesterol. Therefore elevated levels of circulating ApoB...
Apolipoprotein B (ApoB) is the primary component of atherogenic lipoproteins, which transport serum fats and cholesterol. Therefore elevated levels of circulating ApoB are a primary risk factor for cardiovascular disease. During ApoB biosynthesis in the liver and small intestine under nutrient-rich conditions, ApoB cotranslationally translocates into the endoplasmic reticulum (ER) and is lipidated and ultimately secreted. Under lipid-poor conditions, ApoB is targeted for ER-associated degradation (ERAD). Although prior work identified select chaperones that regulate ApoB biogenesis, the contributions of cytoplasmic Hsp40s are undefined. To this end, we screened ApoB-expressing yeast and determined that a class A ER-associated Hsp40, Ydj1, associates with and facilitates the ERAD of ApoB. Consistent with these results, a homologous Hsp40, DNAJA1, functioned similarly in rat hepatoma cells. DNAJA1-deficient cells also secreted hyperlipidated lipoproteins in accordance with attenuated ERAD. In contrast to the role of DNAJA1 during ERAD, DNAJB1-a class B Hsp40-helped stabilize ApoB. Depletion of DNAJA1 and DNAJB1 also led to opposing effects on ApoB ubiquitination. These data represent the first example in which different Hsp40s exhibit disparate effects during regulated protein biogenesis in the ER and highlight distinct roles that chaperones can play on a single ERAD substrate.
Topics: Apolipoprotein B-100; Apolipoproteins B; Endoplasmic Reticulum; Endoplasmic Reticulum-Associated Degradation; HSP40 Heat-Shock Proteins; Lipoproteins; Molecular Chaperones; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Ubiquitination
PubMed: 34910568
DOI: 10.1091/mbc.E21-09-0436 -
FEBS Letters Sep 1996We investigated insulin's effect on intestinal lipid, transport and, particularly, the biogenesis of apolipoproteins crucial to lipoprotein secretion. Adding insulin (3...
We investigated insulin's effect on intestinal lipid, transport and, particularly, the biogenesis of apolipoproteins crucial to lipoprotein secretion. Adding insulin (3 mU) to the serum-free medium of cultured jejunal explants from human fetuses (17-20 weeks) reduced triglyceride and chylomicron production and inhibited apo B-48 and apo B-100 secretion. When apo B mRNA was assayed by RT-PCR and its editing by primer extension, no change was detectable following the addition of insulin. HDL lipid content, apo A-1 synthesis and RNA level were unaffected by insulin. Collectively, these results suggest that the insulin-stimulated decline in intestinal chylomicron output may involve apo B co- or post-translational modifications.
Topics: Abortion, Induced; Apolipoprotein A-I; Apolipoprotein B-100; Apolipoprotein B-48; Apolipoproteins B; DNA Primers; Embryo, Mammalian; Female; Fetus; Gene Expression; Gestational Age; Humans; Insulin; Jejunum; Lipid Metabolism; Lipoproteins; Organ Culture Techniques; Polymerase Chain Reaction; Pregnancy; RNA Editing
PubMed: 8814300
DOI: 10.1016/0014-5793(96)00896-4 -
Frontiers in Endocrinology 2023Non-fasting lipid assessment can help predict cardiovascular disease risks and is linked to multiple diseases, particularly diabetes. The significance of non-fasting...
BACKGROUND
Non-fasting lipid assessment can help predict cardiovascular disease risks and is linked to multiple diseases, particularly diabetes. The significance of non-fasting lipid levels in routine screening and postprandial lipid tests for potential dyslipidemia has not been conclusively determined. Various new lipid-lowering strategies have been developed to improve non-fasting dyslipidemia. Therefore, analysis of scientific outputs over the past decade is essential to reveal trends, hotspots, and frontier areas for future research in this field.
METHODS
The Science Citation Index Expanded in the Web of Science Core Collection database was searched for publications related to non-fasting lipid research from 2012 to 2022. The regional distributions, authors, disciplines, journals, references, and keywords of the studies were analyzed using the bibliometric software VOSviewer and CiteSpace.
RESULTS
A total of 4160 articles and reviews that met the inclusion criteria were included in this study. The output trend was established to be stable and the number of citation indices has been persistently increasing. A total of 104 countries/regions, 4668 organizations, and 20782 authors were involved in this research area. In terms of country, the United States had the largest number of publications (979). The University of Copenhagen was the most productive institution, publishing 148 papers. Professor Børge G Nordestgaard has made the most significant contribution to this field. was the most productive journal while the was the highest co-cited journal. Analysis of co-cited references indicated that lipid-lowering strategies, statin therapy, high-fat meals, insulin resistance, physical exercise, and fructose were hotspots. Analysis of co-cited keywords revealed that apolipoprotein B, especially apolipoprotein B48, is becoming a key research focus. The keywords "gut microbiota" and "meal timing" were the most extensively studied.
CONCLUSION
The causal relationship between non-fasting dyslipidemia and diseases is currently being explored and the standards for non-fasting or postprandial lipid assessment are continuously being updated. Among the hotspots, lipid-lowering strategies are a potential research direction. Apolipoprotein B48, gut microbiota, and chrononutrition are the research frontiers. This initial bibliometric analysis of non-fasting lipids will enable researchers to monitor swift transformations and recognize novel concepts for upcoming research.
Topics: Apolipoprotein B-48; Apolipoproteins B; Bibliometrics; Databases, Factual; Exercise
PubMed: 37152935
DOI: 10.3389/fendo.2023.1136048 -
Gastroenterologie Clinique Et Biologique Dec 2004
Review
Topics: Abetalipoproteinemia; Apolipoproteins B; Chylomicrons; Digestive System Physiological Phenomena; Humans; Hypobetalipoproteinemias; Intestinal Absorption; Intestines; Lipid Metabolism; RNA Editing
PubMed: 15671937
DOI: 10.1016/s0399-8320(04)95219-0