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Journal of Lipid Research

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https://www.readbyqxmd.com/read/28528321/omega-3-fatty-acids-lipids-and-apoe-lipidation-in-alzheimer-s-disease-a-rationale-for-multi-nutrient-dementia-prevention
#1
Marcus O Grimm, Daniel Michaelson, Tobias Hartmann
In the last decade it has become obvious that Alzheimer's disease (AD) is closely linked to changes in lipids or lipid metabolism. One of the main pathological hallmarks of AD is amyloid-β (Aβ) deposition. Aβ is derived from sequential proteolytic processing of the amyloid precursor protein (APP). Interestingly, both, the APP and all APP secretases are transmembrane proteins which cleave APP close to and in the lipid bilayer. Moreover, apolipoprotein E4 (apoE4) has been identified as the most prevalent genetic risk factor for AD...
May 20, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28515139/changes-in-ceramide-metabolism-are-essential-in-madin-darby-canine-kidney-cell-differentiation
#2
Lucila Gisele Pescio, Bruno Jaime Santacreu, Vanina Gisela Lopez, Carlos Humberto Paván, Daniela Judith Romero, Nicolás Octavio Favale, Norma Beatriz Sterin-Speziale
Ceramides and complex sphingolipids with defined acyl-chain lengths play important roles in numerous cell processes. Six ceramide synthase isoenzymes (CerS1-6) are the key enzymes responsible for the production of the diversity of molecular species. In this study, we investigated the changes in sphingolipid metabolism during the differentiation of Madin-Darby Canine Kidney (MDCK) cells. By MALDI TOF TOF MS, we analyzed the molecular species of ceramide (Cer), glucosylceramide (GlcCer), lactosylceramide (LacCer) and sphingomyelin (SM) in non-differentiated and differentiated cells (cultured under hypertonicity)...
May 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28515138/dalcetrapib-and-anacetrapib-differently-impact-hdl-structure-and-function-in-rabbits-and-monkeys
#3
Mathieu R Brodeur, David Rhainds, Daniel Charpentier, Téodora Mihalache-Avram, Mélanie Mecteau, Geneviève Brand, Evelyne Chaput, Anne Perez, Eric J Niesor, Eric Rhéaume, Cyrille Maugeais, Jean-Claude Tardif
Inhibition of cholesteryl ester transfer protein (CETP) increases high density lipoprotein cholesterol (HDL-C) levels. However, circulating CETP level varies and the impact of its inhibition in species with high CETP levels on HDL structure and function remains poorly characterized. This study investigated the effects of dalcetrapib and anacetrapib, the two CETP inhibitors (CETPi) currently tested in large clinical outcome trials, on HDL particle subclass distribution and cholesterol efflux capacity of serum in rabbits and monkeys...
May 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28512139/a-genome-wide-association-meta-analysis-on-lipoprotein-a-concentrations-adjusted-for-apolipoprotein-a-isoforms
#4
Salome Mack, Stefan Coassin, Rico Rueedi, Noha A Yousri, Ilkka Seppälä, Christian Gieger, Sebastian Schönherr, Lukas Forer, Gertraud Erhart, Pedro Marques-Vidal, Janina Ried, Gerard Waeber, Sven Bergmann, Doreen Dähnhardt, Andrea Stöckl, Olli T Raitakari, Mika Kähönen, Annette Peters, Thomas Meitinger, Konstantin Strauch, Ludmilla Kedenko, Bernhard Paulweber, Terho Lehtimäki, Steven C Hunt, Peter Vollenweider, Claudia Lamina, Florian Kronenberg
High lipoprotein(a) [Lp(a)] concentrations are an independent risk factor for cardiovascular outcomes. Concentrations are strongly influenced by apo(a) KIV repeat isoforms. We aimed to identify genetic loci associated with Lp(a) concentrations using data from five genome-wide association studies (n=13,781). We identified 48 independent SNPs in the LPA and 1 SNP in the APOE gene region to be significantly associated with Lp(a) concentrations. We also adjusted for apo(a) isoforms to identify loci affecting Lp(a) levels independently from them, which resulted in 31 SNPs (30 in the LPA, 1 in the APOE gene region)...
May 16, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28507038/high-affinity-pan-specific-monoclonal-antibodies-that-target-cysteinyl-leukotrienes-and-show-efficacy-in-an-acute-model-of-colitis
#5
Ashlee N King, Jonathan K Fleming, Stephanie S Knapik, Barbara Visentin, Jonathan M Wojciak, Tom Huxford
Cysteinyl leukotrienes (CysLTs) are a small family of biological signaling lipids produced by active leukocytes that contribute to diverse inflammatory disease states as a consequence of their engagement with dedicated G protein-coupled receptors. Immunization of mice with a CysLT-modified hapten carrier protein yielded novel monoclonal antibodies that display variable binding affinity to CysLTs. Solution binding assays indicated differing specificities among the antibodies tested, with antibody 10G4 displaying a preference for leukotriene C4 (LTC4)...
May 15, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28490444/inhibiting-glucosylceramide-synthase-exacerbates-cisplatin-induced-acute-kidney-injury
#6
Tess V Dupre, Mark A Doll, Parag P Shah, Cierra N Sharp, Deanna Siow, Judit Megyesi, James Shayman, Alicja Bielwska, Jacek Bielawski, Levi J Beverly, Maria Hernandez-Corbacho, Christopher J Clarke, Ashley J Snider, Rick G Schnellmann, Lina M Obeid, Yusuf A Hannun, Leah J Siskind
Acute kidney injury (AKI), resulting from chemotherapeutic agents such as cisplatin, remains an obstacle in the treatment of cancer. Cisplatin-induced AKI involves apoptotic and necrotic cell death, pathways regulated by sphingolipids such as ceramide and glucosylceramide. Results from this study indicate that C57BL/6J mice treated with cisplatin had increased ceramide and hexosylceramide levels in the renal cortex 72 h following cisplatin treatment. Pre-treatment of mice with inhibitors of acid sphingomyelinase and de novo ceramide synthesis (amitriptyline and myriocin, respectively) prevented accumulation of ceramides and hexosylceramide in the renal cortex and protected from cisplatin-induced AKI...
May 10, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28487312/complete-deletion-of-cd39-is-atheroprotective-in-apolipoprotein-e-deficient-mice
#7
Marco De Giorgi, Keiichi Enjyoji, Gordon Jiang, Eva Csizmadia, Shuji Mitsuhashi, Richard J Gumina, Ryszard T Smolenski, Simon C Robson
CD39 scavenges extracellular ATP and ADP, ultimately generating adenosine, a nucleoside, which has anti-inflammatory effects in the vasculature. We have evaluated the role of CD39 in the development of atherosclerosis in hyperlipidemic mice. ApoE KO (Cd39+/+/ApoE-/-) and Cd39/ApoE double knockout (Cd39-/-/ApoE-/-, DKO) mice were maintained on chow or Western diet for up to 20 weeks before evaluation of atherosclerotic lesions. We found that DKO mice exhibited significantly less atherosclerotic lesions than ApoE KO mice, irrespective of diet...
May 9, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28476858/mutating-a-conserved-cysteine-in-gpihbp1-reduces-amounts-of-gpihbp1-in-capillaries-and-abolishes-lpl-binding
#8
Christopher M Allan, Cris J Jung, Mikael Larsson, Patrick J Heizer, Yiping Tu, Norma P Sandoval, Tiffany Ly P Dang, Rachel S Jung, Anne P Beigneux, Pieter J de Jong, Loren G Fong, Stephen G Young
Mutation of conserved cysteines in proteins of the Ly6 family cause human disease-chylomicronemia in the case of GPIHBP1 and paroxysmal nocturnal hemoglobinuria in the case of CD59. A mutation in a conserved cysteine in CD59 prevented the protein from reaching the surface of blood cells. In contrast, mutation of conserved cysteines in human GPIHBP1 had little effect on GPIHBP1 trafficking to the surface of cultured CHO cells. The latter findings were somewhat surprising and raised questions about whether CHO cell studies accurately model the fate of mutant GPIHBP1 proteins in vivo...
May 5, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28476857/apolipoprotein-a-ii-alters-the-proteome-of-human-lipoproteins-and-enhances-cholesterol-efflux-from-abca1
#9
John T Melchior, Scott E Street, Allison B Andraski, Jeremy D Furtado, Frank M Sacks, Rebecca L Shute, Emily I Greve, Debi K Swertfeger, Hailong Li, Amy S Shah, L Jason Lu, W Sean Davidson
High density lipoproteins (HDL) are a heterogeneous family of particles that vary in size, composition and function. The structure of most HDL is maintained by two scaffold proteins, apolipoprotein (apo)A-I and apoA-II, but up to 95 other accessory proteins have been found associated with the particles. Recent evidence suggests these accessory proteins are distributed across various subspecies and drive specific biological functions. Unfortunately, our understanding of the molecular composition of such subspecies is limited...
May 5, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28473603/increased-hepatic-mitochondrial-fa-oxidation-leads-to-lower-tg-levels-in-rat-liver-and-plasma-and-is-associated-with-upregulation-of-uncoupling-proteins-and-downregulation-of-apolipoprotein-c-iii
#10
Carine Lindquist, Bodil Bjørndal, Christine Renate Rossmann, Deusdedit Tusubira, Asbjørn Svardal, Gro Vatne Røsland, Karl Johan Tronstad, Seth Hallström, Rolf Kristian Berge
Hepatic mitochondrial function, APOC-III and LPL are potential targets for TG lowering drugs. After three weeks of dietary treatment with the compound 2-(tridec-12 -yn-1-ylthio) acetic acid (1-triple TTA), the hepatic mitochondrial FA oxidation increased more than 5-fold in male Wistar rats. Gene expression analysis in liver showed significant downregulation of APOC-III, and upregulation of LPL and the VLDL receptor. This led to lower hepatic (53 %) and plasma (73 %) TG levels. Concomitantly liver-specific biomarkers related to mitochondrial biogenesis and function (mitochondrial DNA, citrate synthase activity and cytochrome c and Tfam gene expression) were elevated...
May 4, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28465289/association-between-serum-phospholipid-fatty-acids-levels-and-adiposity-in-mexican-women
#11
Elom K Aglago, Carine Biessy, Gabriela Torres-Mejía, Angélica Angeles-Llerenas, Marc J Gunter, Isabelle Romieu, Veronique Chajès
Fatty acids have been postulated to impact adiposity, but few epidemiological studies addressing this hypothesis have been conducted. This study investigated the association between serum phospholipid fatty acids (S-PLFA) and indicators of obesity. Body mass index (BMI) and waist-to-hip ratio (WHR) were collected from 372 healthy Mexican women included as controls in a case-control study. S-PLFA percentages were determined through gas chromatography. Desaturation indices, SCD-16, SCD-18, FADS1 and FADS2, biomarkers of endogenous metabolism, were proxied respectively as 16:1n-7/16:0, 18:1n-9/18:0, 20:4n-6/20:3n-6 and 22:6n-3/20:5n-3...
May 2, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28455387/will-the-real-bile-acid-sulfotransferase-please-stand-up-identification-of-sult2a8-as-a-major-hepatic-bile-acid-sulfonating-enzyme-in-mice
#12
Paul A Dawson, Kenneth D R Setchell
No abstract text is available yet for this article.
April 28, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28442498/identification-and-characterization-of-a-novel-ppar%C3%AE-regulated-and-7%C3%AE-hydroxyl-bile-acid-preferring-cytosolic-sulfotransferase-ml-stl-sult2a8
#13
Lu Feng, Yee-Lok Yuen, Jian Xu, Xing Liu, Martin Yan-Chun Chan, Kai Wang, Wing-Ping Fong, Wing-Tai Cheung, Susanna Sau-Tuen Lee
PPARα has been known to play a pivotal role in orchestrating lipid, glucose, and amino acid metabolism via transcriptional regulation of its target genes expression during energy deprivation. Recent evidence also suggesting PPARα is involved in bile acid metabolism, but how PPARα modulates the homeostasis of bile acids during fasting is still not clear. In a mechanistic study aiming to dissect the spectrum of PPARα target genes involved in metabolic response to fasting, we identified a novel mouse gene (herein named mL-STL) which shared extensive homology to Sult2a subfamily of a superfamily of cytosolic sulfotransferases, implying its potential function in sulfonation...
April 25, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28442497/an-in-silico-model-of-retinal-cholesterol-dynamics-rcd-model-insights-into-the-pathophysiology-of-dry-age-related-macular-degeneration
#14
Seyedeh Maryam Zekavat, James Lu, Cyrille Maugeais, Norman A Mazer
We developed an in-silico mathematical model of retinal cholesterol (Ch) dynamics (RCD) to quantify the physiological rate of Ch turnover in the rod outer segment (ROS), the lipoprotein transport mechanisms by which Ch enters and leaves the outer retina, and the rates of drusen growth and macrophage-mediated clearance in dry Age-Related Macular Degeneration (AMD). Based on existing experimental data and mechanistic hypotheses, we estimate the Ch turnover rate in the ROS to be 1-6 pg/mm2/min, dependent on the rate of Ch recycling in the outer retina, and find comparable rates for LDL receptor-mediated endocytosis of Ch by the retinal pigment epithelium (RPE), ABCA1-mediated Ch transport from the RPE to outer retina, ABCA1-mediated Ch efflux from the RPE to choroid, and the secretion of 70 nm ApoB-Ch particles from the RPE...
April 25, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28432183/anacetrapib-driven-triglyceride-lowering-explained-the-fortuitous-role-of-cetp-in-the-intravascular-catabolism-of-triglyceride-rich-lipoproteins
#15
Amanda L Brown, J Mark Brown
No abstract text is available yet for this article.
April 21, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28420706/common-structural-features-of-cholesterol-binding-sites-in-crystallized-soluble-proteins
#16
Anna N Bukiya, Alejandro M Dopico
Cholesterol-protein interactions are essential for the architectural organization of cell membranes and for lipid metabolism. While cholesterol-sensing motifs in transmembrane proteins have been identified, little is known about cholesterol recognition by soluble proteins. We reviewed the structural characteristics of binding sites for cholesterol and cholesterol sulfate from crystallographic structures available in the Protein Data Bank. This analysis unveiled key features of cholesterol-binding sites that are present in either all or the majority of sites: i) the cholesterol molecule is generally positioned between protein domains that have an organized secondary structure; ii) the cholesterol hydroxyl/sulfo group is often partnered by Asn, Gln and/or Tyr while the hydrophobic part of cholesterol interacts with Leu, Ile, Val and/or Phe; iii) cholesterol hydrogen-bonding partners are often found on alpha-helices while amino acids that interact with cholesterol hydrophobic core have a slight preference for beta-strands and secondary structure-lacking protein areas; iv) the steroid C21 and 26 constitute the ″hot spots″ most often seen for steroid-protein hydrophobic interactions; v) common ″cold spots″ are C8, 9, 10, 13 and 17, at which contacts with the proteins were not detected...
April 18, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28420705/synthesis-of-neutral-ether-lipid-monoalkyl-diacylglycerol-madag-by-lipid-acyltransferases
#17
Zhengping Ma, Joelle M Onorato, Luping Chen, David W Nelson, Chi-Liang Eric Yen, Dong Cheng
In mammals, ether lipids exert a wide spectrum of signaling and structural functions such as stimulation of immune responses, anti-tumor activities and enhancement of sperm functions. Abnormal accumulation of monoalkyl-diacylglycerol (MADAG) was found in Wolman disease, a human genetic disorder defined by a deficiency in lysosomal acid lipase. In the current study, we found that among the 9 recombinant human lipid acyltransferases examined, DGAT1, DGAT2, MGAT2, MGAT3, AWAT2/MFAT and DC3 were able to use 1-monoalkylglycerol (1-MAkG) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG)...
April 18, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28420704/influence-of-hdl-particles-on-cell-cholesterol-efflux-under-various-pathological-conditions
#18
Bela F Asztalos, Katalin V Horvath, Michael Mehan, Yuya Yokota, Ernst J Schaefer
It has been reported that low cell-cholesterol efflux capacity (CEC) of HDL is an independent risk factor for CVD. To better understand CEC regulation, we measured ABCA1- and SR-BI-dependent cell-cholesterol efflux, HDL anti-oxidative capacity, HDL particles, lipids, and inflammatory- and oxidative-stress markers in 122 subjects with elevated plasma levels of TG, serum amyloid A (SAA), fibrinogen, myeloperoxidase (MPO), or β-sitosterol and in 146 controls. In controls, there were strong positive correlations between ABCA1-dependent cholesterol efflux and small prebeta-1 concentrations (R2=0...
April 18, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28420658/simple-and-rapid-biochemical-method-to-synthesize-labeled-or-unlabeled-phosphatidylinositol-species
#19
Satu Hänninen, Krishna Chaithanya Batchu, Kati Hokynar, Pentti Somerharju
Phosphatidylinositol (PI) is the precursor of many important signaling molecules in eukaryotic cells and, most probably, PI also has important functions in cellular membranes. However, these functions are poorly understood, which is largely due to that (i) only few PI species with specific acyl chains are available commercially and (ii) there are no simple methods to synthesize such species. Here, we present a simple biochemical method to synthetize a variety of labeled or unlabeled PI species from corresponding commercially available phosphatidylcholines...
April 18, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28416579/inflammatory-stimuli-induce-acyl-coa-thioesterase-7-and-remodeling-of-phospholipids-containing-unsaturated-long-%C3%A2-c20-acyl-chains-in-macrophages
#20
Valerie Z Wall, Shelley Barnhart, Farah Kramer, Jenny E Kanter, Anuradha Vivekanandan-Giri, Subramaniam Pennathur, Chiara Bolego, Jessica M Ellis, Miguel A Gijón, Michael J Wolfgang, Karin E Bornfeldt
Acyl-CoA thioesterase 7 (ACOT7) is an intracellular enzyme that converts acyl-CoAs to free fatty acids. ACOT7 is induced by lipopolysaccharide (LPS), thus we investigated downstream effects of LPS-induced induction of ACOT7 and its role in inflammatory settings in myeloid cells. Enzymatic thioesterase activity assays in wildtype and ACOT7-deficient macrophage lysates indicated that endogenous ACOT7 contributes a significant fraction of total acyl-CoA thioesterase activity towards C20:4-CoA, C20:5-CoA and C22:6-CoA, but contributes little activity towards shorter acyl-CoA species...
April 17, 2017: Journal of Lipid Research
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