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https://www.readbyqxmd.com/read/27919362/the-effect-of-omega-3-carboxylic-acids-on-apolipoprotein-ciii-containing-lipoproteins-in-severe-hypertriglyceridemia
#1
Allyson M Morton, Jeremy D Furtado, Jane Lee, William Amerine, Michael H Davidson, Frank M Sacks
BACKGROUND: Lipoprotein subspecies containing apoCIII adversely affect cardiovascular disease (CVD) risk; for example, low density lipoprotein (LDL) with apoCIII is a stronger CVD predictor than LDL without apoCIII. The Epanova for Lowering Very High Triglycerides (EVOLVE) trial showed that Epanova (omega-3 carboxylic acids [OM3-CA]) significantly lowered TG and apoCIII but raised LDL-C. However, it is unknown what subspecies of LDL were affected by treatment. OBJECTIVE: To determine how lipoprotein subspecies are affected by omega-3 fatty acid treatment, we studied the effect of OM3-CA on apoCIII concentrations in high density lipoprotein (HDL), LDL, and very low density lipoprotein (VLDL) and on the concentrations of subspecies of HDL, LDL, and VLDL that contain or do not contain apoCIII...
November 2016: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/27875339/apolipoprotein-ciii-is-a-new-player-in-diabetes
#2
Lisa Juntti-Berggren, Per-Olof Berggren
PURPOSE OF REVIEW: Type-1 and type-2 diabetes are diseases with an increasing number of patients and a complex, multifactorial pathogenesis. Apolipoprotein (apo) CIII is increased in both types of diabetes and interventions preventing the increase have effects on the development of diabetes. RECENT FINDINGS: ApoCIII affects intracellular Ca-handling by activating voltage-gated Ca-channels. ApoCIII is produced within the pancreatic islets and it increases in parallel with the development of insulin resistance and type-2 diabetes...
November 21, 2016: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/27611192/effects-of-a-plant-sterol-or-stanol-enriched-mixed-meal-on-postprandial-lipid-metabolism-in-healthy-subjects
#3
Sabine Baumgartner, Ronald P Mensink, Jogchum Plat
BACKGROUND: Evidence is increasing that plant sterols and stanols not only lower fasting serum low-density lipoprotein concentrations, but also those of triglycerides (TG). Insight into effects of these components on postprandial TG metabolism, an emerging risk factor for cardiovascular disease, is missing. OBJECTIVE: Our objective was to examine the 8-hour postprandial response after consuming plant sterol or stanol enriched margarine as part of a mixed meal. METHODS: This postprandial study was part of a randomized crossover study in which 42 subjects consumed plant sterol enriched (3 g/d plant sterols), plant stanol enriched (3 g/d plant stanols), and control margarines for 4 weeks...
2016: PloS One
https://www.readbyqxmd.com/read/27155393/loganin-inhibits-the-inflammatory-response-in-mouse-3t3l1-adipocytes-and-mouse-model
#4
Yang Li, Zheng Li, Lei Shi, Chenxu Zhao, Bingyu Shen, Ye Tian, Haihua Feng
Atherosclerosis is a chronic inflammatory disease of the vascular walls. ApoCIII is an independent factor which promotes atherosclerotic processes. This study aimed to investigate whether Loganin administration inhibits the inflammatory response in vitro and in vivo. In the apoCIII-induced mouse adipocytes, the levels of cytokines, including TNF-α, MCP-1 and IL-6 were determined by enzyme-linked immunosorbent assay and their gene expressions were measured through RT-PCR. The phosphorylation of nuclear factor-κB (NF-κB) proteins was analyzed by Western blotting...
May 4, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/26970521/severe-hypertriglyceridemia-does-not-protect-from-ischemic-brain-injury-in-gene-modified-hypertriglyceridemic-mice
#5
Yong Chen, Ping Liu, Rong Qi, Yu-Hui Wang, George Liu, Chun Wang
Hypertriglyceridemia (HTG) is a weak risk factor in primary ischemic stroke prevention. However, clinical studies have found a counterintuitive association between a good prognosis after ischemic stroke and HTG. This "HTG paradox" requires confirmation and further explanation. The aim of this study was to experimentally assess this paradox relationship using the gene-modified mice model of extreme HTG. We first used the human Apolipoprotein CIII transgenic (Tg-ApoCIII) mice and non-transgenic (Non-Tg) littermates to examine the effect of HTG on stroke...
May 15, 2016: Brain Research
https://www.readbyqxmd.com/read/26900642/effect-of-leptin-administration-on-circulating-apolipoprotein-ciii-levels-in-patients-with-lipodystrophy
#6
Andrea Kassai, Ranganath Muniyappa, Amy E Levenson, Mary F Walter, Brent S Abel, Michael Ring, Simeon I Taylor, Sudha B Biddinger, Monica C Skarulis, Phillip Gorden, Rebecca J Brown
Patients with lipodystrophy had elevated apolipoprotein CIII (apoCIII) compared to healthy controls. ApoCIII did not change with leptin treatment despite significant reductions in serum triglyceride.
April 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/26848137/reduction-in-lipoprotein-associated-apoc-iii-levels-following-volanesorsen-therapy-phase-2-randomized-trial-results
#7
Xiaohong Yang, Sang-Rok Lee, Yun-Seok Choi, Veronica J Alexander, Andres Digenio, Qingqing Yang, Yury I Miller, Joseph L Witztum, Sotirios Tsimikas
Elevated apoC-III levels predict increased cardiovascular risk when present on LDL and HDL particles. We developed novel high-throughput chemiluminescent ELISAs that capture apoB, lipoprotein (a) [Lp(a)], and apoA-I in plasma and then detect apoC-III on these individual lipoproteins as apoCIII-apoB, apoCIII-Lp(a), and apoCIII-apoAI complexes, respectively. We assessed the effects on these complexes of placebo or 100-300 mg volanesorsen, a generation 2.0+ antisense drug that targets apoC3 mRNA in patients with hypertriglyceridemia, including familial chylomicronemia syndrome (n = 3), volanesorsen monotherapy (n = 51), and as add-on to fibrate (n = 26), treated for 85 days and followed for 176 days...
April 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/26773160/multiplexed-peptide-analysis-for-kinetic-measurements-of-major-human-apolipoproteins-by-lc-ms-ms
#8
Mikaël Croyal, Fanta Fall, Véronique Ferchaud-Roucher, Maud Chétiveaux, Yassine Zaïr, Khadija Ouguerram, Michel Krempf, Estelle Nobécourt
A multiplexed assay was developed by MS to analyze, in a single run, six major human Apos involved in lipoprotein metabolism: ApoA-I, ApoA-II, ApoB100, ApoC-II, ApoC-III, and ApoE. This method was validated in vivo in six subjects who received a 14 h constant infusion of [5,5,5-(2)H3]L-leucine at 10 μM/kg/h. Plasma lipoprotein fractions were isolated from collected blood samples and were digested with trypsin. Proteotypic peptides were subsequently analyzed by LC/MS/MS. Enrichment measurement data were compared with those obtained by the standard method using GC/MS...
March 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/26452348/the-association-of-hdl-apociii-with-coronary-heart-disease-and-the-effect-of-statin-treatment-on-it
#9
Xiaowei Xiong, Hong Liu, Lu Hua, Hui Zhao, Dongxue Wang, Yishi Li
BACKGROUND: Apolipoprotein CIII (apoCIII) is considered to impair the anti-atherogenic effect of high density lipoprotein (HDL) in coronary heart disease (CHD) patients, and apoCIII content in HDL (HDL-apoCIII) predicts CHD more accurately. However, the relationship between HDL-apoCIII and CHD, and the effect of statin treatment on HDL-apoCIII are still unclear. The aims of the study are to establish the association of HDL-apoCIII with CHD, and investigate the effect of statin treatment on HDL-apoCIII in CHD patients...
2015: Lipids in Health and Disease
https://www.readbyqxmd.com/read/26301570/tryptophan-probes-reveal-residue-specific-phospholipid-interactions-of-apolipoprotein-c-iii
#10
Candace M Pfefferkorn, Robert L Walker, Yi He, James M Gruschus, Jennifer C Lee
Apolipoproteins are essential human proteins for lipid metabolism. Together with phospholipids, they constitute lipoproteins, nm to μm sized particles responsible for transporting cholesterol and triglycerides throughout the body. To investigate specific protein-lipid interactions, we produced and characterized three single-Trp containing apolipoprotein C-III (ApoCIII) variants (W42 (W54F/W65F), W54 (W42F/W65F), W65 (W42F/W54F)). Upon binding to phospholipid vesicles, wild-type ApoCIII adopts an α-helical conformation (50% helicity) as determined by circular dichroism spectroscopy with an approximate apparent partition constant of 3×10(4) M(-1)...
November 2015: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/26280786/ledipasvir-sofosbuvir-treatment-of-hepatitis-c-virus-is-associated-with-reduction-in-serum-apolipoprotein-levels
#11
RANDOMIZED CONTROLLED TRIAL
Z M Younossi, E Elsheikh, M Stepanova, L Gerber, F Nader, L M Stamm, D M Brainard, J G McHutchinson
The interaction of lipoproteins with hepatitis C virus (HCV) has pathogenic and therapeutic implications. Our aim was to evaluate changes in the apolipoprotein profile of patients with chronic hepatitis C during and after successful cure with ledipasvir and sofosbuvir (LDV/SOF) with and without ribavirin (RBV). One hundred HCV genotype 1 patients who had achieved SVR-12 after treatment with 12 weeks of LDV/SOF ± RBV were selected from the ION-1 clinical trial. Frozen serum samples from baseline, end of treatment and week 4 of follow-up were used to assay apolipoproteins (apoAI, apoAII, apoB, apoCII, apoCIII, apoE) using the Multiplex platform to assess for changes in the apolipoprotein levels...
December 2015: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/26160324/aggravated-restenosis-and-atherogenesis-in-apociii-transgenic-mice-but-lack-of-protection-in-apociii-knockouts-the-effect-of-authentic-triglyceride-rich-lipoproteins-with-and-without-apociii
#12
Haibo Li, Yingchun Han, Rong Qi, Yuhui Wang, Xiaohong Zhang, Maomao Yu, Yin Tang, Mengyu Wang, Ya-Nan Shu, Wei Huang, Xinfeng Liu, Brian Rodrigues, Mei Han, George Liu
AIM: Previously, our group and others have demonstrated a causative relationship between severe hypertriglyceridaemia and atherogenesis in mice. Furthermore, clinical investigations have shown high levels of plasma Apolipoprotein C-III (ApoCIII) associated with hypertriglyceridaemia and even cardiovascular disease. However, it remains unclear whether ApoCIII affects restenosis in vivo, and whether such an effect is mediated by ApoCIII alone, or in combination with hypertriglyceridaemia...
September 1, 2015: Cardiovascular Research
https://www.readbyqxmd.com/read/25994465/-mutations-of-apoc3-gene-metabolism-of-triglycerides-and-reduction-of-ischemic-cardiovascular-events
#13
Angela Pirillo, Alberico Luigi Catapano
A direct relationship between high plasma triglyceride (TG) levels and increased risk of cardiovascular disease has been shown in several studies. TG are present in the blood associated with different lipoprotein classes, including hepatically-derived very low density lipoproteins (VLDL) and intestinally-derived chylomicrons. Lipoprotein lipase (LPL) is a key enzyme that hydrolyzes TG, releasing free fatty acids that accumulate in peripheral tissues and remnant lipoproteins, that are then cleared by the liver...
May 2015: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/25969427/reduced-high-density-lipoprotein-cholesterol-in-severe-hypertriglyceridemic-apociii-transgenic-mice-via-lowered-hepatic-apoai-synthesis
#14
Yingchun Han, Rong Qi, George Liu
Clinical and epidemiological investigations confirm that patients with loss-of-function mutations (R19X, etc.) in Apolipoprotein CIII (ApoCIII) showed beneficial lipid profile including decreased plasma triglyceride and increased high density lipoprotein (HDL) levels. However, whether HDL level would be reduced in hypertriglyceridemia (HTG) induced by high ApoCIII expression has not been demonstrated yet. Here we showed, ApoCIII transgenic mice (ApoCIIItg) displayed severe HTG and had significantly lower HDL level...
July 10, 2015: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/25944794/fty720-attenuates-acute-pancreatitis-in-hypertriglyceridemic-apolipoprotein-ciii-transgenic-mice
#15
Jinjiao Liu, Pengfei Xu, Ling Zhang, Abudurexiti Kayoumu, Yunan Wang, Mengyu Wang, Mingming Gao, Xiaohong Zhang, Yuhui Wang, George Liu
Hypertriglyceridemic pancreatitis (HTGP) is often encountered clinically as a common form of recurrent acute pancreatitis (AP). It is important to evaluate the management of severe hypertriglyceridemia (HTG) or anti-inflammation in the prophylaxis of HTGP in the clinic. FTY720 (2-amino-2[2-(4-octylphenyl) ethyl]-1, 3-propanediol) is a new anti-inflammatory agent with low toxicity and reported to ameliorate lung injury with pancreatitis in rat. We evaluated its protective affection on AP induced by seven hourly intraperitoneal injection of cerulein in apolipoprotein CIII transgenic mice with severe HTG...
September 2015: Shock
https://www.readbyqxmd.com/read/25941406/apolipoprotein-ciii-links-islet-insulin-resistance-to-%C3%AE-cell-failure-in-diabetes
#16
Karin Åvall, Yusuf Ali, Ingo B Leibiger, Barbara Leibiger, Tilo Moede, Meike Paschen, Andrea Dicker, Elisabetta Daré, Martin Köhler, Erwin Ilegems, Midhat H Abdulreda, Mark Graham, Rosanne M Crooke, Vanessa S Y Tay, Essam Refai, Stefan K Nilsson, Stefan Jacob, Lars Selander, Per-Olof Berggren, Lisa Juntti-Berggren
Insulin resistance and β-cell failure are the major defects in type 2 diabetes mellitus. However, the molecular mechanisms linking these two defects remain unknown. Elevated levels of apolipoprotein CIII (apoCIII) are associated not only with insulin resistance but also with cardiovascular disorders and inflammation. We now demonstrate that local apoCIII production is connected to pancreatic islet insulin resistance and β-cell failure. An increase in islet apoCIII causes promotion of a local inflammatory milieu, increased mitochondrial metabolism, deranged regulation of β-cell cytoplasmic free Ca(2+) concentration ([Ca(2+)]i) and apoptosis...
May 19, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/25859267/maternal-inheritance-of-severe-hypertriglyceridemia-impairs-glucose-metabolism-in-offspring
#17
Ya-Hong Ma, Caiguo Yu, Abudurexiti Kayoumu, Xin Guo, Zhili Ji, George Liu
Maternally inherited familial hypercholesterolemia (FH) impairs glucose metabolism and increases cardiovascular risks in the offspring to a greater degree than paternal inherited FH. However, it remains unknown whether hypertriglyceridemia affects glucose metabolism via inheritance. In this study, we sought to compare the impact of maternally and paternally inherited hypertriglyceridemia on glucose and lipid metabolism in mice. ApoCIII transgenic mice with severe hypertriglyceridemia were mated with non-transgenic control mice to obtain 4 types of offspring: maternal non-transgenic control and maternal transgenic offspring, and paternal control and paternal transgenic offspring...
April 2015: Journal of Biomedical Research
https://www.readbyqxmd.com/read/25787436/-85-or-fetal-triglyceride-concentrations-and-apolipoprotein-ciii-glycosylation-sialylation-in-iugr
#18
Ulrich Pecks, Isabelle Kirschner, Manja Wölter, Nicolai Maass, Michael O Glocker, Werner Rath
OBJECTIVES: Apolipoprotein CIII (apoCIII) is involved in triglyceride metabolism. More specifically, desialylation of apoCIII results in the inhibition of triglyceride catabolism. We therefore hypothesized that glycosylation/sialylation of apoCIII correlates with the elevated triglyceride concentrations observed in cord blood of IUGR fetuses. METHODS: Venous cord blood samples of 36 IUGR and 49 preterm and term born controls (CTRL) were analyzed. Peak areas of the different apoCIII species (apoCIII0, apoCIII0', apoCIII1, apoCIII2) were determined by MALDI ToF mass spectrometry (MS)...
January 2015: Pregnancy Hypertension
https://www.readbyqxmd.com/read/25267016/adipocyte-cell-size-free-fatty-acids-and-apolipoproteins-are-associated-with-non-alcoholic-liver-injury-progression-in-severely-obese-patients
#19
Alexander Wree, Martin Schlattjan, Lars P Bechmann, Thierry Claudel, Jan-Peter Sowa, Tatjana Stojakovic, Hubert Scharnagl, Harald Köfeler, Hideo A Baba, Guido Gerken, Ariel E Feldstein, Michael Trauner, Ali Canbay
PURPOSE: Obesity is a modern pandemic with continuous expansion and represents an independent risk factor for non-alcoholic fatty liver disease (NAFLD), the most common liver disease in westernized countries. The crosstalk between adipose tissue and the liver is key to the development of NAFLD. PROCEDURES: Therefore, in an observational study blood, visceral adipose tissue and liver tissue were obtained from 93 severely obese patients with a mean age of 43 years and mean BMI of 52 kg/m2 at the time of weight loss surgery...
December 2014: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/25255477/inhibition-of-apociii-the-next-pcsk9
#20
REVIEW
Sophie J Bernelot Moens, Julian C van Capelleveen, Erik S G Stroes
PURPOSE OF REVIEW: Recent large Mendelian randomization studies associate loss-of-function mutations in apolipoprotein CIII (APOCIII) with low levels of triglycerides and decreased incidence of cardiovascular disease. With ample in-vitro and in-vivo evidence for a role of apoCIII in lipoprotein lipase-mediated triglyceride clearance and remnant removal, it is, thus, an attractive target for the treatment of hypertriglyceridemia and the prevention of cardiovascular disease. This review evaluates the current position of apoCIII in clinical practice and provides a glimpse into the future in terms of treatment options...
December 2014: Current Opinion in Lipidology
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