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Lawrence P. Aggerbeck - One of the best experts on this subject based on the ideXlab platform.
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anderson s disease chylomicron retention disease in a japanese patient with uniparental disomy 7 and a normal sar1b gene protein coding sequence
Orphanet Journal of Rare Diseases, 2011Co-Authors: Tomoo Okada, Michio Miyashita, Junji Fukuhara, Marie Elisabeth Samsonbouma, Masahiko Sugitani, Takahiro Ueno, Lawrence P. AggerbeckAbstract:Background Anderson's Disease (AD)/Chylomicron Retention Disease (CMRD) is a rare hereditary hypocholesterolemic disorder characterized by a malabsorption syndrome with steatorrhea, failure to thrive and the absence of chylomicrons and Apolipoprotein B48 post-prandially. All patients studied to date exhibit a mutation in the SAR1B gene, which codes for an essential component of the vesicular coat protein complex II (COPII) necessary for endoplasmic reticulum to Golgi transport. We describe here a patient with AD/CMRD, a normal SAR1B gene protein coding sequence and maternal uniparental disomy of chromosome 7 (matUPD7).
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Anderson's disease/chylomicron retention disease in a Japanese patient with uniparental disomy 7 and a normal SAR1B gene protein coding sequence
Orphanet journal of rare diseases, 2011Co-Authors: Tomoo Okada, Michio Miyashita, Junji Fukuhara, Masahiko Sugitani, Takahiro Ueno, Marie-elisabeth Samson-bouma, Lawrence P. AggerbeckAbstract:Background Anderson's Disease (AD)/Chylomicron Retention Disease (CMRD) is a rare hereditary hypocholesterolemic disorder characterized by a malabsorption syndrome with steatorrhea, failure to thrive and the absence of chylomicrons and Apolipoprotein B48 post-prandially. All patients studied to date exhibit a mutation in the SAR1B gene, which codes for an essential component of the vesicular coat protein complex II (COPII) necessary for endoplasmic reticulum to Golgi transport. We describe here a patient with AD/CMRD, a normal SAR1B gene protein coding sequence and maternal uniparental disomy of chromosome 7 (matUPD7).
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Anderson's disease/chylomicron retention disease in a Japanese patient with uniparental disomy 7 and a normal SAR1B gene protein coding sequence.
Orphanet Journal of Rare Diseases, 2011Co-Authors: Tomoo Okada, Michio Miyashita, Junji Fukuhara, Masahiko Sugitani, Takahiro Ueno, Marie-elisabeth Samson-bouma, Lawrence P. AggerbeckAbstract:UNLABELLED: ABSTRACT: BACKGROUND: Anderson's Disease (AD)/Chylomicron Retention Disease (CMRD) is a rare hereditary hypocholesterolemic disorder characterized by a malabsorption syndrome with steatorrhea, failure to thrive and the absence of chylomicrons and Apolipoprotein B48 post-prandially. All patients studied to date exhibit a mutation in the SAR1B gene, which codes for an essential component of the vesicular coat protein complex II (COPII) necessary for endoplasmic reticulum to Golgi transport. We describe here a patient with AD/CMRD, a normal SAR1B gene protein coding sequence and maternal uniparental disomy of chromosome 7 (matUPD7). METHODS AND RESULTS: The patient, one of two siblings of a Japanese family, had diarrhea and steatorrhea beginning at five months of age. There was a white duodenal mucosa upon endoscopy. Light and electron microscopy showed that the intestinal villi were normal but that they had lipid laden enterocytes containing accumulations of lipid droplets in the cytoplasm and lipoprotein-size particles in membrane bound structures. Although there were decreased amounts in plasma of total- and low-density lipoprotein cholesterol, Apolipoproteins AI and B and vitamin E levels, the triglycerides were normal, typical of AD/CMRD. The presence of low density lipoproteins and Apolipoprotein B in the plasma, although in decreased amounts, ruled out abetalipoproteinemia. The parents were asymptomatic with normal plasma cholesterol levels suggesting a recessive disorder and ruling out familial hypobetalipoproteinemia. Sequencing of genomic DNA showed that the 8 exons of the SAR1B gene were normal. Whole genome SNP analysis and karyotyping revealed matUPD7 with a normal karyotype. In contrast to other cases of AD/CMRD which have shown catch-up growth following vitamin supplementation and a fat restricted diet, our patient exhibits continued growth delay and other aspects of the matUPD7 and Silver-Russell Syndrome phenotypes. CONCLUSIONS: This patient with AD/CMRD has a normal SAR1B gene protein coding sequence which suggests that factors other than the SAR1B protein may be crucial for chylomicron secretion. Further, this patient exhibits matUPD7 with regions of homozygosity which might be useful for elucidating the molecular basis of the defect(s) in this individual. The results provide novel insights into the relation between phenotype and genotype in these diseases and for the mechanisms of secretion in the intestine.
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Anderson's Disease (Chylomicron Retention Disease)
Encyclopedia of Endocrine Diseases, 2004Co-Authors: Nathalie Berriot-varoqueaux, Marie-elisabeth Samson-bouma, Lawrence P. AggerbeckAbstract:Anderson's disease and chylomicron retention disease (OMIM#246700) are terms used for very similar, if not identical, rare autosomal recessive hereditary hypocholesterolemic disorders. The disease most frequently presents in infants and is characterized by a lipid malabsorption syndrome with steatorrhea, chronic diarrhea and growth retardation. Normal fasting serum triglyceride levels combined with the absence of Apolipoprotein B48 and chylomicrons after a fat load is characteristic of the disease. In many cases, mutations have been found in the gene coding for the SAR1B GTPase (OMIM*607690), which participates in COPII mediated intra-cellular trafficking, the effects of which are believed to disrupt chylomicron assembly/secretion.
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Apolipoprotein B48 glycosylation in abetalipoproteinemia and anderson s disease
Gastroenterology, 2001Co-Authors: Nathalie Berriotvaroqueaux, Hayssam A Dannoura, Alain Moreau, Nicole Verthier, Agnes Sassolas, Guillaume Cadiot, A Lachaux, A Munck, J Schmitz, Lawrence P. AggerbeckAbstract:Abstract Background & Aims: Abetalipoproteinemia and Anderson's disease are hereditary lipid malabsorption syndromes. In abetalipoproteinemia, lipoprotein assembly is defective because of mutations in the microsomal triglyceride transfer protein. Here, we evaluated the intracellular transport of Apolipoprotein B48 to localize the defect in Anderson's disease. Methods: Asparagine-linked oligosaccharide processing of Apolipoprotein B48 in normal and affected individuals was determined by the endoglycosidase H and F sensitivities of the protein after metabolic labeling of intestinal explants in organ culture. Cell ultrastructure was evaluated with electron microscopy. Results: In Anderson's disease as in normal individuals, there was a time-dependent transformation of high mannose endoglycosidase H–sensitive oligosaccharides, of endoplasmic reticulum origin, to complex endoglycosidase H–resistant oligosaccharides, added in the Golgi network. In contrast, despite the translocation of Apolipoprotein B48 into the endoplasmic reticulum in patients with abetalipoproteinemia and in biopsies treated with Brefeldin A, which blocks anterograde transport between the endoplasmic reticulum and the Golgi network, there was no transformation of endoglycosidase H–sensitive oligosaccharides. Conclusions: In abetalipoproteinemia and Anderson's disease, Apolipoprotein B48 is completely translocated into the endoplasmic reticulum, but only in Anderson's disease is the protein transported to the Golgi apparatus. This suggests that Anderson's disease is caused by a post-Golgi cargo-specific secretion defect. GASTROENTEROLOGY 2001;121:1101-1108
John C L Mamo - One of the best experts on this subject based on the ideXlab platform.
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increased risk of cardiovascular disease in type 1 diabetes arterial exposure to remnant lipoproteins leads to enhanced deposition of cholesterol and binding to glycated extracellular matrix proteoglycans
Diabetic Medicine, 2011Co-Authors: Rabban Mangat, Donna F Vine, Jennifer E Lambert, M T Clandinin, Jenny W Su, Ye Wang, Richard R E Uwiera, Josephine M Forbes, Mark E Cooper, John C L MamoAbstract:Aims To determine fasting and postprandial metabolism of Apolipoprotein B48 (apoB48) remnant lipoproteins in subjects with Type 1 diabetes and the relationship to progressive cardiovascular disease, and to investigate the impact of remnant lipoprotein cholesterol accumulation associated with arterial wall biglycan using a rodent model of Type 1 diabetes.Methods Normolipidaemic subjects (n = 9) with long-standing Type 1 diabetes (and advanced cardiovascular disease) and seven healthy control subjects were studied. Fasting and postprandial apoB48 concentration was determined following a sequential meal challenge. A rodent model of streptozotocin-induced diabetes was used to investigate the ex vivo retention of fluorescent-conjugated remnants. Binding of remnant lipoproteins to human recombinant biglycan was assessed in vitro.Results A significantly higher concentration of fasting plasma apoB48 remnants was observed in patients with Type 1 diabetes compared with control subjects. Patients with Type 1 diabetes exhibited a greater total plasma apoB48 area under the curve (AUC) and an increased incremental AUC following a second sequential meal compared with control subjects. The arterial retention of remnants ex vivo and associated cholesterol was increased sevenfold in Type 1 diabetes rats relative to controls. Remnants were shown to bind with significant affinity to human biglycan in vitro and a further 2.3-fold increased binding capacity was observed with glycated biglycan. Remnants were shown to colocalize with both arterial biglycan and glycated matrix proteins in the Type 1 diabetes rodent model.Conclusion Impaired metabolism of remnant lipoproteins associated with enhanced binding to proteoglycans appears to contribute to the arterial cholesterol deposition in Type 1 diabetes. Our findings support the hypothesis that impaired remnant metabolism may contribute to accelerated progression of atherosclerosis in the hyperglycaemic and insulin-deficient state. © 2010 The Authors. Diabetic Medicine
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Prior exercise does not affect chylomicron particle number following a mixed meal of moderate fat content
Lipids in Health and Disease, 2007Co-Authors: Anthony P James, Karin Slivkoff-clark, John C L MamoAbstract:Background A single session of exercise has been reported to reduce fasting and postprandial triacylglycerol concentrations on the subsequent day. It is possible that exercise also reduces chylomicron particle number, which may underlie the observed reduction in postprandial triacylglycerol concentration. In the present study we aimed to determine whether a single session of exercise reduces fasting and postprandial chylomicron particle number on the subsequent day. In a randomised crossover design eight lean and healthy male and female subjects attended two postprandial testing days. On the previous day the subjects either performed 90 minutes of moderate intensity exercise or did not perform any exercise. Fasting blood samples were then collected prior to ingestion of a moderate fat mixed meal (0.44 g fat, 0.94 g carbohydrate, 0.27 g protein/kg body weight), blood was then collected after 1 h, 2 h, 4 h, 6 h, and 8 h. Results The fasting and postprandial Apolipoprotein B48 concentration (marker of chylomicron particle number) was not affected by prior exercise. However exercise reduced fasting triacylglycerol concentration by 16% ( P < 0.05) and there was a trend towards a reduction in the total area under the postprandial triacylglycerol curve (23%; P = 0.053). However when corrected for baseline concentration postprandial triacylglycerol concentration was not affected by prior exercise. Conclusion A single session of exercise of moderate intensity and 90 minutes duration reduces fasting triacylglycerol levels, however fasting and postprandial chylomicron particle number was unaffected. Furthermore it appears that previously observed reductions in postprandial triacylglycerol levels following exercise are only mediated following consumption of high, non-physiologically relevant doses of fat.
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effect of atorvastatin on Apolipoprotein B48 metabolism and low density lipoprotein receptor activity in normolipidemic patients with coronary artery disease
Metabolism-clinical and Experimental, 2003Co-Authors: Cheryl A Danestewart, Gerald F Watts, Sebely Pal, Dick C Chan, Peter L Thompson, Joseph Hung, John C L MamoAbstract:Abstract We aimed to examine postprandial dyslipidemia in normolipidemic patients with coronary artery disease (CAD) and the effects of treatment with an hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor (atorvastatin). Subjects with angiographicaly established CAD were randomized to treatment for 12 weeks with 80 mg/d atorvastatin or placebo and the effects on markers of postprandial lipoproteins and low-density lipoprotein (LDL)-receptor binding determined. LDL-receptor binding was determined in mononuclear cells, as a surrogate for hepatic activity. Fasting levels of cholesterol ( P P 48 ( P = .019), remnant-like particle-cholesterol (RLP-C) ( P = .032), and total postprandial apoB 48 area under the curve (AUC) ( P = .013) significantly decreased with atorvastatin compared with placebo. Atorvastatin also significantly increased LDL-receptor binding activity ( P 48 ( r = .80, P = .01). We report that aberrations in chylomicron metabolism in normolipidemic CAD subjects are correctable with atorvastatin by a mechanism involving increased LDL-receptor activity. This effect may, in part, explain the cardiovascular benefit of statins used in clinical trials of CAD patients with normal lipid levels.
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intimal retention of cholesterol derived from Apolipoprotein b100 and Apolipoprotein B48 containing lipoproteins in carotid arteries of watanabe heritable hyperlipidemic rabbits
Arteriosclerosis Thrombosis and Vascular Biology, 2003Co-Authors: Spencer D Proctor, John C L MamoAbstract:Objectives— The arterial retention of Apolipoprotein (apo) B100- and apoB48-containing lipoproteins was simultaneously determined in a rabbit model of human hypercholesterolemia using 3D confocal microscopy. Methods and Results— Lipoproteins containing apoB100 (LDL) and apoB48 (chylomicron remnants) were differentially conjugated with fluorophores and simultaneously perfused at equivalent concentrations under physiological conditions in situ through carotid vessels of Watanabe heritable hyperlipidemic rabbits and compared with controls. Retention of lipoproteins was defined as the amount remaining after an extensive washout phase. LDL and chylomicron remnants were both retained, primarily within the subendothelial space. Without a concomitant increase in exposure to lipoproteins, we found a marked increase in the retention of cholesterol within the intima of Watanabe heritable hyperlipidemic rabbits compared with controls, specifically because of increased entrapment of apoB48-containing lipoproteins. Conclusions— Collectively, our data suggest that hypercholesterolemia induced as a consequence of LDL receptor deficiency differentially influences retention of LDL and of chylomicron remnants.
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arterial retention of Apolipoprotein B48 and b100 containing lipoproteins in atherogenesis
Current Opinion in Lipidology, 2002Co-Authors: Spencer D Proctor, Donna F Vine, John C L MamoAbstract:Purpose of reviewThe ‘response to retention’ hypothesis of atherosclerosissuggests that the arterial deposition of cholesterol is directlyproportional to the concentration of circulating plasmalipoproteins. However, there is increasing evidence to supportthe concept that specific lipoproteins may be preferentiallyretained within the arterial wall, possibly as a result of greateraffinity for cell surface and extracellular matrices.Recent findingsRecently, key studies have provided insight into mechanismsinvolved in the interaction of Apolipoprotein B (apoB)-containinglipoproteins with extracellular matrices. In addition, novelmethods and innovative experimental design has enabled us todifferentiate between the delivery, retention and efflux ofapoB
Khosrow Adeli - One of the best experts on this subject based on the ideXlab platform.
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intestinal scavenger receptor class b type i as a novel regulator of chylomicron production in healthy and diet induced obese states
American Journal of Physiology-gastrointestinal and Liver Physiology, 2015Co-Authors: Marsel Lino, Sarah Farr, Christopher A Baker, Mark T Fuller, Bernardo L Trigatti, Khosrow AdeliAbstract:The small intestine contributes to diabetic dyslipidemia through the overproduction of Apolipoprotein B48 (apoB48)-containing chylomicron particles. An important regulator of chylomicron generation...
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glucagon like peptide 2 glp 2 stimulates postprandial chylomicron production and postabsorptive release of intestinal triglyceride storage pools via induction of nitric oxide signaling in male hamsters and mice
Endocrinology, 2015Co-Authors: Joanne Hsieh, Sarah Farr, Karin Trajcevski, Chris Baker, Elizabeth J Lake, Jennifer Taher, Jahangir Iqbal, Mahmood M Hussain, Khosrow AdeliAbstract:The intestinal overproduction of Apolipoprotein B48 (apoB48)-containing chylomicron particles is a common feature of diabetic dyslipidemia and contributes to cardiovascular risk in insulin resistant states. We previously reported that glucagon-like peptide-2 (GLP-2) is a key endocrine stimulator of enterocyte fat absorption and chylomicron output in the postprandial state. GLP-2's stimulatory effect on chylomicron production in the postabsorptive state has been confirmed in human studies. The mechanism by which GLP-2 regulates chylomicron production is unclear, because its receptor is not expressed on enterocytes. We provide evidence for a key role of nitric oxide (NO) in mediating the stimulatory effects of GLP-2 during the postprandial and postabsorptive periods. Intestinal chylomicron production was assessed in GLP-2-treated hamsters administered the pan-specific NO synthase (NOS) inhibitor L-NG-nitroarginine methyl ester (L-NAME), and in GLP-2-treated endothelial NOS knockout mice. L-NAME blocked GLP-...
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cinnamon extract inhibits the postprandial overproduction of Apolipoprotein B48 containing lipoproteins in fructose fed animals
Journal of Nutritional Biochemistry, 2009Co-Authors: Marilyn M Polansky, Yuzo Sato, Khosrow Adeli, Richard A AndersonAbstract:Abstract We have reported previously that a cinnamon extract (CE), high in type A polyphenols, prevents fructose feeding-induced decreases in insulin sensitivity and suggested that improvements of insulin sensitivity by CE were attributable, in part, to enhanced insulin signaling. In this study, we examined the effects of CE on postprandial Apolipoprotein (apo) B-48 increase in fructose-fed rats, and the secretion of apoB48 in freshly isolated intestinal enterocytes of fructose-fed hamsters. In an olive oil loading study, a water-soluble CE (Cinnulin PF, 50 mg/kg body weight, orally) decreased serum triglyceride (TG) levels and the over production of total- and TG-rich lipoprotein-apoB48. In ex vivo 35 S labeling study, significant decreases were also observed in apoB48 secretion into the media in enterocytes isolated from fructose-fed hamsters. We also investigated the molecular mechanisms of the effects of CE on the expression of genes of the insulin signaling pathway [insulin receptor (IR), IR substrate (IRS)1, IRS2 and Akt1], and lipoprotein metabolism [microsomal TG transfer protein (MTP), sterol regulatory element-binding protein (SREBP1c) in isolated primary enterocytes of fructose-fed hamsters, using quantitative real-time polymerase chain reaction. The CE reversed the expression of the impaired IR, IRS1, IRS2 and Akt1 mRNA levels and inhibited the overexpression of MTP and SREBP1c mRNA levels of enterocytes. Taken together, our data suggest that the postprandial hypertriglycerides and the overproduction of apoB48 can be acutely inhibited by a CE by a mechanism involving improvements of insulin sensitivity of intestinal enterocytes and regulation of MTP and SREBP1c levels. We present both in vivo and ex vivo evidence that a CE improves the postprandial overproduction of intestinal apoB48-containing lipoproteins by ameliorating intestinal insulin resistance and may be beneficial in the control of lipid metabolism.
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glucagon like peptide 2 increases intestinal lipid absorption and chylomicron production via cd36
Gastroenterology, 2009Co-Authors: Joanne Hsieh, Chris Baker, Christine Longuet, Adriano Maida, Jasmine Bahrami, Elaine Xu, Patricia L Brubaker, Daniel J Drucker, Khosrow AdeliAbstract:Background & Aims Excessive postprandial lipemia is a prevalent condition that results from intestinal oversecretion of Apolipoprotein B48 (apoB48)-containing lipoproteins. Glucagon-like peptide-2 (GLP-2) is a gastrointestinal-derived intestinotropic hormone that links nutrient absorption to intestinal structure and function. We investigated the effects of GLP-2 on intestinal lipid absorption and lipoprotein production. Methods Intestinal lipid absorption and chylomicron production were quantified in hamsters, wild-type mice, and Cd36 −/− mice infused with exogenous GLP-2. Newly synthesized apoB48 was metabolically labelled in primary hamster jejunal fragments. Fatty acid absorption was measured, and putative fatty acid transporters were assessed by immunoblotting. Results Human GLP-2 increased secretion of the triglyceride (TG)-rich lipoprotein (TRL)-apoB48 following oral administration of olive oil to hamsters; TRL and cholesterol mass each increased 3-fold. Fast protein liquid chromatography profiling indicated that GLP-2 stimulated secretion of chylomicron/very low-density lipoprotein-sized particles. Moreover, GLP-2 directly stimulated apoB48 secretion in jejunal fragments cultured ex vivo, increased expression of fully glycosylated cluster of differentiation 36/fatty acid translocase (CD36), and induced intestinal absorption of [ 3 H]triolein. The ability of GLP-2 to increase intestinal lipoprotein production was lost in Cd36 −/− mice. Conclusions GLP-2 stimulates intestinal apoB48-containing lipoprotein secretion, possibly through increased lipid uptake, via a pathway that requires CD36. These findings suggest that GLP-2 represents a nutrient-dependent signal that regulates intestinal lipid absorption and the assembly and secretion of TRLs from intestinal enterocytes.
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glucagon like peptide 2 increases intestinal lipid absorption and chylomicron production via cd36
Gastroenterology, 2009Co-Authors: Joanne Hsieh, Christine Longuet, Adriano Maida, Jasmine Bahrami, Patricia L Brubaker, Daniel J Drucker, Christopher Baker, Khosrow AdeliAbstract:Background & Aims Excessive postprandial lipemia is a prevalent condition that results from intestinal oversecretion of Apolipoprotein B48 (apoB48)-containing lipoproteins. Glucagon-like peptide-2 (GLP-2) is a gastrointestinal-derived intestinotropic hormone that links nutrient absorption to intestinal structure and function. We investigated the effects of GLP-2 on intestinal lipid absorption and lipoprotein production. Methods Intestinal lipid absorption and chylomicron production were quantified in hamsters, wild-type mice, and Cd36 −/− mice infused with exogenous GLP-2. Newly synthesized apoB48 was metabolically labelled in primary hamster jejunal fragments. Fatty acid absorption was measured, and putative fatty acid transporters were assessed by immunoblotting. Results Human GLP-2 increased secretion of the triglyceride (TG)-rich lipoprotein (TRL)-apoB48 following oral administration of olive oil to hamsters; TRL and cholesterol mass each increased 3-fold. Fast protein liquid chromatography profiling indicated that GLP-2 stimulated secretion of chylomicron/very low-density lipoprotein-sized particles. Moreover, GLP-2 directly stimulated apoB48 secretion in jejunal fragments cultured ex vivo, increased expression of fully glycosylated cluster of differentiation 36/fatty acid translocase (CD36), and induced intestinal absorption of [ 3 H]triolein. The ability of GLP-2 to increase intestinal lipoprotein production was lost in Cd36 −/− mice. Conclusions GLP-2 stimulates intestinal apoB48-containing lipoprotein secretion, possibly through increased lipid uptake, via a pathway that requires CD36. These findings suggest that GLP-2 represents a nutrient-dependent signal that regulates intestinal lipid absorption and the assembly and secretion of TRLs from intestinal enterocytes.
Spencer D Proctor - One of the best experts on this subject based on the ideXlab platform.
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impaired postprandial metabolism of Apolipoprotein B48 containing remnant particles in normolipidemic subjects with brittle type 1 diabetes
Diabetes Care, 2009Co-Authors: Jennifer E Lambert, M T Clandinin, Spencer D ProctorAbstract:Impaired metabolism of intestinally derived chylomicron remnants has been implicated in the development of atherosclerosis among normolipidemic patients with coronary heart disease (1,2) and, indeed, in other conditions associated with increased vascular disease such as obesity, metabolic syndrome, type 2 diabetes, and familial hypercholesterolemia (3–5). However, the role of these particles in the increased atherosclerotic risk associated with type 1 diabetes is unclear. No studies to date have examined Apolipoprotein (apo)B48, a specific marker of chylomicron particle number, in the human type 1 diabetic population. Nine normolipidemic subjects (five male and four female) with brittle type 1 diabetes and seven healthy normolipidemic …
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Apolipoprotein B48 a novel marker of metabolic risk in overweight children
Biochemical Society Transactions, 2007Co-Authors: M M U Nzekwu, Geoff D C Ball, Mary M Jetha, Christian Beaulieu, Spencer D ProctorAbstract:Clinical studies in adults indicate there is a positive and significant association between insulin resistance, dyslipidaemia, fasting intestinally derived lipoproteins [via apoB48 (Apolipoprotein B48)] and visceral fat. All of these factors contribute to increased risk of CVD (cardiovascular disease). Since little is known about postprandial dyslipidaemia in overweight children, we sought to compare fasting levels of apoB48 with the HOMA-IR (homoeostasis model assessment of insulin resistance) score, classic lipid profile and VAT (visceral adipose tissue). Pre-pubertal, overweight boys and girls were recruited from the wider-Edmonton area (Alberta). Body composition was determined using both dual-energy X-ray absorptiometry and MRI (magnetic resonance imaging). Fasting apoB48 was quantified in plasma using an adapted SDS/PAGE immunoblotting technique, and insulin, glucose, TC (total cholesterol), TAG (triacylglycerol), LDL (low-density lipoprotein) and HDL (high-density lipoprotein) were determined by calorimetric assay. In this overweight sample, we observed elevated fasting apoB48 concentrations, greater than the normal adult range. In addition, apoB48 was significantly related to HOMA-IR and TAG levels. Although apoB48 was positively correlated with TC and LDL and negatively associated with HDL, these relationships did not achieve significance. Our ongoing MRI analysis reveals a positive relationship between apoB48 and VAT volume. To our knowledge, this is the first study to report apoB48 concentrations in overweight pre-pubertal children. Thus this article will provide a brief rationale for our study and its methodology.
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impaired postprandial Apolipoprotein B48 metabolism in the obese insulin resistant jcr la cp rat increased atherogenicity for the metabolic syndrome
Atherosclerosis, 2007Co-Authors: Donna F Vine, Ryusuke Takechi, James C Russell, Spencer D ProctorAbstract:Aim: Postprandial lipaemia is a significant contributor to the development of dyslipidaemia and cardiovascular disease, which has more recently been shown as a potential risk factor for obesity and pre-diabetes. Clinically however, the diagnosis of early insulin-resistance remains confounded due to the fact that aberrations in lipid metabolism are not often readily identified using classic indicators of hypercholesterolemia (i.e. LDL). Methods: In this study, we assessed the metabolism of Apolipoprotein-B48 (apoB48)-containing lipoproteins in an animal model of obesity and insulin-resistance, the JCR:LA-cp rat. The contribution of lipoproteins from the intestine was assessed by measuring plasma apoB48 concentration in the postprandial period following an oral fat load. Plasma apoB48 was measured by improved enhanced chemiluminescent detection and other biochemical parameters measured by established analysis. Results: Fasting concentrations of plasma apoB48, postprandial apoB48 area under the curve (AUC), as well as incremental-AUC (iAUC), were all significantly greater in the obese phenotype compared to lean controls. Fasting apoB48 correlated significantly with apoB48-iAUC, triglyceride (TG)-iAUC and insulin-iAUC. In addition, there was a highly significant association with fasting insulin and the postprandial ratio of TG:apoB48, a relationship not often detected in humans during insulin-resistance. Conclusions/interpretation: We conclude that the JCR:LA-cp rat can be used as a model of postprandial lipemia to explore chylomicron metabolism during the onset and development of insulin-resistance, including the increased cardiovascular complications of the metabolic syndrome.
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intimal retention of cholesterol derived from Apolipoprotein b100 and Apolipoprotein B48 containing lipoproteins in carotid arteries of watanabe heritable hyperlipidemic rabbits
Arteriosclerosis Thrombosis and Vascular Biology, 2003Co-Authors: Spencer D Proctor, John C L MamoAbstract:Objectives— The arterial retention of Apolipoprotein (apo) B100- and apoB48-containing lipoproteins was simultaneously determined in a rabbit model of human hypercholesterolemia using 3D confocal microscopy. Methods and Results— Lipoproteins containing apoB100 (LDL) and apoB48 (chylomicron remnants) were differentially conjugated with fluorophores and simultaneously perfused at equivalent concentrations under physiological conditions in situ through carotid vessels of Watanabe heritable hyperlipidemic rabbits and compared with controls. Retention of lipoproteins was defined as the amount remaining after an extensive washout phase. LDL and chylomicron remnants were both retained, primarily within the subendothelial space. Without a concomitant increase in exposure to lipoproteins, we found a marked increase in the retention of cholesterol within the intima of Watanabe heritable hyperlipidemic rabbits compared with controls, specifically because of increased entrapment of apoB48-containing lipoproteins. Conclusions— Collectively, our data suggest that hypercholesterolemia induced as a consequence of LDL receptor deficiency differentially influences retention of LDL and of chylomicron remnants.
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arterial retention of Apolipoprotein B48 and b100 containing lipoproteins in atherogenesis
Current Opinion in Lipidology, 2002Co-Authors: Spencer D Proctor, Donna F Vine, John C L MamoAbstract:Purpose of reviewThe ‘response to retention’ hypothesis of atherosclerosissuggests that the arterial deposition of cholesterol is directlyproportional to the concentration of circulating plasmalipoproteins. However, there is increasing evidence to supportthe concept that specific lipoproteins may be preferentiallyretained within the arterial wall, possibly as a result of greateraffinity for cell surface and extracellular matrices.Recent findingsRecently, key studies have provided insight into mechanismsinvolved in the interaction of Apolipoprotein B (apoB)-containinglipoproteins with extracellular matrices. In addition, novelmethods and innovative experimental design has enabled us todifferentiate between the delivery, retention and efflux ofapoB
Tomoo Okada - One of the best experts on this subject based on the ideXlab platform.
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anderson s disease chylomicron retention disease in a japanese patient with uniparental disomy 7 and a normal sar1b gene protein coding sequence
Orphanet Journal of Rare Diseases, 2011Co-Authors: Tomoo Okada, Michio Miyashita, Junji Fukuhara, Marie Elisabeth Samsonbouma, Masahiko Sugitani, Takahiro Ueno, Lawrence P. AggerbeckAbstract:Background Anderson's Disease (AD)/Chylomicron Retention Disease (CMRD) is a rare hereditary hypocholesterolemic disorder characterized by a malabsorption syndrome with steatorrhea, failure to thrive and the absence of chylomicrons and Apolipoprotein B48 post-prandially. All patients studied to date exhibit a mutation in the SAR1B gene, which codes for an essential component of the vesicular coat protein complex II (COPII) necessary for endoplasmic reticulum to Golgi transport. We describe here a patient with AD/CMRD, a normal SAR1B gene protein coding sequence and maternal uniparental disomy of chromosome 7 (matUPD7).
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Anderson's disease/chylomicron retention disease in a Japanese patient with uniparental disomy 7 and a normal SAR1B gene protein coding sequence
Orphanet journal of rare diseases, 2011Co-Authors: Tomoo Okada, Michio Miyashita, Junji Fukuhara, Masahiko Sugitani, Takahiro Ueno, Marie-elisabeth Samson-bouma, Lawrence P. AggerbeckAbstract:Background Anderson's Disease (AD)/Chylomicron Retention Disease (CMRD) is a rare hereditary hypocholesterolemic disorder characterized by a malabsorption syndrome with steatorrhea, failure to thrive and the absence of chylomicrons and Apolipoprotein B48 post-prandially. All patients studied to date exhibit a mutation in the SAR1B gene, which codes for an essential component of the vesicular coat protein complex II (COPII) necessary for endoplasmic reticulum to Golgi transport. We describe here a patient with AD/CMRD, a normal SAR1B gene protein coding sequence and maternal uniparental disomy of chromosome 7 (matUPD7).
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Anderson's disease/chylomicron retention disease in a Japanese patient with uniparental disomy 7 and a normal SAR1B gene protein coding sequence.
Orphanet Journal of Rare Diseases, 2011Co-Authors: Tomoo Okada, Michio Miyashita, Junji Fukuhara, Masahiko Sugitani, Takahiro Ueno, Marie-elisabeth Samson-bouma, Lawrence P. AggerbeckAbstract:UNLABELLED: ABSTRACT: BACKGROUND: Anderson's Disease (AD)/Chylomicron Retention Disease (CMRD) is a rare hereditary hypocholesterolemic disorder characterized by a malabsorption syndrome with steatorrhea, failure to thrive and the absence of chylomicrons and Apolipoprotein B48 post-prandially. All patients studied to date exhibit a mutation in the SAR1B gene, which codes for an essential component of the vesicular coat protein complex II (COPII) necessary for endoplasmic reticulum to Golgi transport. We describe here a patient with AD/CMRD, a normal SAR1B gene protein coding sequence and maternal uniparental disomy of chromosome 7 (matUPD7). METHODS AND RESULTS: The patient, one of two siblings of a Japanese family, had diarrhea and steatorrhea beginning at five months of age. There was a white duodenal mucosa upon endoscopy. Light and electron microscopy showed that the intestinal villi were normal but that they had lipid laden enterocytes containing accumulations of lipid droplets in the cytoplasm and lipoprotein-size particles in membrane bound structures. Although there were decreased amounts in plasma of total- and low-density lipoprotein cholesterol, Apolipoproteins AI and B and vitamin E levels, the triglycerides were normal, typical of AD/CMRD. The presence of low density lipoproteins and Apolipoprotein B in the plasma, although in decreased amounts, ruled out abetalipoproteinemia. The parents were asymptomatic with normal plasma cholesterol levels suggesting a recessive disorder and ruling out familial hypobetalipoproteinemia. Sequencing of genomic DNA showed that the 8 exons of the SAR1B gene were normal. Whole genome SNP analysis and karyotyping revealed matUPD7 with a normal karyotype. In contrast to other cases of AD/CMRD which have shown catch-up growth following vitamin supplementation and a fat restricted diet, our patient exhibits continued growth delay and other aspects of the matUPD7 and Silver-Russell Syndrome phenotypes. CONCLUSIONS: This patient with AD/CMRD has a normal SAR1B gene protein coding sequence which suggests that factors other than the SAR1B protein may be crucial for chylomicron secretion. Further, this patient exhibits matUPD7 with regions of homozygosity which might be useful for elucidating the molecular basis of the defect(s) in this individual. The results provide novel insights into the relation between phenotype and genotype in these diseases and for the mechanisms of secretion in the intestine.
