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Journal of Lipid Research

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https://www.readbyqxmd.com/read/28432183/anacetrapib-driven-triglyceride-lowering-explained-the-fortuitous-role-of-cetp-in-the-intravascular-catabolism-of-triglyceride-rich-lipoproteins
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28413163/angptl8-requires-angptl3-to-inhibit-lipoprotein-lipase-and-plasma-triglyceride-clearance
#7
Jorge F Haller, Ivory J Mintah, Lisa M Shihanian, Panayiotis Stevis, David Buckler, Corey A Alexa-Braun, Sandra Kleiner, Serena Banfi, Jonathan C Cohen, Helen H Hobbs, George D Yancopoulos, Andrew J Murphy, Viktoria Gusarova, Jesper Gromada
Angiopoietin-like protein 3 (ANGPTL3) and ANGPTL8 are secreted proteins and inhibitors of lipoprotein lipase (LPL)-mediated plasma triglyceride (TG) clearance. It is unclear how these two ANGPTL proteins interact to regulate LPL activity. ANGPTL3 inhibits LPL activity and increase serum TG in mice independent of ANGPTL8. These effects could be reversed with an ANGPTL3 blocking antibody. Previously, it was shown that ANGPTL8 requires ANGPTL3 expression to increase plasma TG levels. Here we show that the ability of ANGPTL8 to block LPL activity and increase serum TG does not rely on inhibitory activity of ANGPTL3...
April 15, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28412693/feeding-angptl4-mice-trans-fat-promotes-foam-cell-formation-in-mesenteric-lymph-nodes-without-leading-to-ascites
#8
Antwi Boasiako Oteng, Asmita Bhattacharya, Susanne Brodesser, Ling Qi, Nguan Soon Tan, Sander Kersten
ANGPTL4 regulates plasma triglyceride levels by inhibiting lipoprotein lipase. Inactivation of ANGPTL4 decreases plasma triglycerides and reduces risk of coronary artery disease. Unfortunately, targeting ANGPTL4 for the therapeutic management of dyslipidemia and atherosclerosis is hampered by the observation that mice and monkeys in which ANGPTL4 is inactivated exhibit lipid accumulation in mesenteric lymph nodes. In mice these pathological events exclusively unfold upon feeding a high saturated fatty acid diet and are followed by an ultimately lethal pro-inflammatory response and chylous ascites...
April 15, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28411199/impact-of-fabp1-scp-2-scp-x-gene-ablation-tko-on-hepatic-phytol-metabolism-in-mice
#9
Stephen M Storey, Huan Huang, Avery L McIntosh, Gregory G Martin, Ann B Kier, Friedhelm Schroeder
Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x (Scp-2/Scp-x) and liver fatty acid binding protein (Fabp1) gene products facilitate hepatic uptake and metabolism of lipotoxic dietary phytol. However, interpretation of physiological function in mice singly gene ablated in the Scp-2/Scp-x has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: i) An ANS displacement assay showed that neither SCP-2 nor L-FABP bound phytol, but both had high affinity for its metabolite, phytanic acid; ii) GC/MS studies with phytol-fed wild-type (WT) and Fabp1/Scp-2/SCP-x gene ablated (TKO) mice showed that TKO exacerbated hepatic accumulation of phytol metabolites in vivo in females and less so in males...
April 14, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28404641/nlrp3-inflammasome-as-a-novel-target-for-docosahexaenoic-acid-metabolites-to-abrogate-glomerular-injury
#10
Guangbi Li, Zhida Chen, Owais M Bhat, Qinghua Zhang, Justine M Abais-Battad, Sabena M Conley, Joseph K Ritter, Pin-Lan Li
The NOD-like receptor containing pyrin domain 3 (NLRP3) inflammasome has been implicated in podocyte injury and glomerular sclerosis during hyperhomocysteinemia (hHcys). However, it remains unclear whether NLRP3 inflammasome can be a therapeutic target for treatment of hHcys-induced kidney injury. Given that docosahexaenoic acid (DHA) metabolites-resolvins have potent anti-inflammatory effects, the present study tested whether the prototype resolvin D1 (RvD1) and 17S-hydroxy DHA (17S-HDHA), an intermediate product abrogate hHcys-induced podocyte injury by targeting the NLRP3 inflammasome...
April 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28404640/comprehensive-evaluation-of-the-bactericidal-activities-of-free-bile-acids-in-the-large-intestine-of-humans-and-rodents
#11
Masamichi Watanabe, Satoru Fukiya, Atsushi Yokota
In addition to functioning as detergents that aid digestion of dietary lipids in the intestine, some bile acids have been shown to exhibit antimicrobial activity. However, detailed information on the bactericidal activities of the diverse molecular species of bile acid in humans and rodents is largely unknown. Here, we investigated the toxicity of 14 typical human and rodent free bile acids (FBAs) by monitoring intracellular pH, membrane integrity, and viability of a human intestinal bacterium, Bifidobacterium breve JCM 1192(T), upon exposure to these FBAs...
April 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28404639/cholesterol-crystallization-within-hepatocyte-lipid-droplets-and-its-role-in-murine-nash
#12
George N Ioannou, Savitha Subramanian, Alan Chait, W Geoffrey Haigh, Matthew M Yeh, Geoffrey C Farrell, Sum P Lee, Christopher Savard
We recently reported that cholesterol crystals form in hepatocyte lipid droplets (LDs) in human and experimental NASH. Herein, we assigned wild-type C57BL/6J mice to a high-fat (15%) diet for 6 months supplemented with 0%, 0.25%, 0.5%, 0.75%, or 1% dietary cholesterol. Increasing dietary cholesterol led to cholesterol loading of the liver, but not adipose tissue, resulting in fibrosing steatohepatitis at a dietary cholesterol concentration ≥0.5%, whereas mice on lower cholesterol diets developed only simple steatosis...
April 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28404638/kidney-triglyceride-accumulation-in-the-fasted-mouse-is-dependent-upon-serum-free-fatty-acids
#13
Diego Scerbo, Ni-Huiping Son, Alaa Sirwi, Lixia Zeng, Kelli M Sas, Vincenza Cifarelli, Gabriele Schoiswohl, Lesley-Ann Huggins, Namrata Gumaste, Yunying Hu, Subramaniam Pennathur, Nada A Abumrad, Erin E Kershaw, M Mahmood Hussain, Katalin Susztak, Ira J Goldberg
Lipid accumulation is a pathological feature of every type of kidney injury. Despite this striking histological feature, physiological accumulation of lipids in the kidney is poorly understood. We studied whether the accumulation of lipids in the fasted kidney are derived from lipoproteins or non-esterified fatty acids (NEFAs). With overnight fasting, kidneys accumulated triglyceride but had reduced levels of ceramide and glycosphingolipid species. Fasting led to a nearly 5-fold increase in kidney uptake of plasma [14C]oleic acid...
April 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28404637/surfactant-inhibits-atp-induced-release-of-interleukin-1%C3%AE-via-nicotinic-acetylcholine-receptors
#14
Soeren Backhaus, Anna Zakrzewicz, Katrin Richter, Jelena Damm, Sigrid Wilker, Gabriele Fuchs-Moll, Mira Kuellmar, Andreas Hecker, Ivan Manzini, Clemens Ruppert, J Michael McIntosh, Winfried Padberg, Veronika Grau
Interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine of innate immunity involved in host defense. High systemic IL-1β; levels, however, cause life-threatening inflammatory diseases including systemic inflammatory response syndrome. In response to various danger signals, pro-IL-1β; is synthesized and stays in the cytoplasm unless a second signal such as extracellular ATP activates the inflammasome, which enables processing and release of mature IL-1β. As pulmonary surfactant is known for its anti-inflammatory properties, we hypothesize that surfactant inhibits ATP-induced release of IL-1β...
April 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28396342/increased-maternal-and-fetal-cholesterol-efflux-capacity-and-placental-cyp27a1-expression-in-pre-eclampsia
#15
Hiten D Mistry, Lesia O Kurlak, Yosef T Mansour, Line Zurkinden, Markus G Mohaupt, Geneviève Escher
Pre-eclampsia is a pregnancy-specific condition, leading to increased cardiovascular risk in later life. A decrease in cholesterol efflux capacity is linked to cardiovascular disease. We hypothesised that, in pre-eclampsia there would be a disruption of maternal/fetal plasma to efflux cholesterol as well as differences in the concentrations of both placental sterol 27-hydroxylase (CYP27A1) and apoA1-binding-protein (AIBP). Total, HDL- and ABCA1-mediated cholesterol efflux were performed with maternal and fetal plasma from women with pre-eclampsia and normotensive controls (both n=17)...
April 10, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28392500/metabolism-and-proteomics-of-large-and-small-dense-ldl-in-combined-hyperlipidemia-effects-of-rosuvastatin
#16
Nuntakorn Thongtang, Margaret R Diffenderfer, Esther M M Ooi, P Hugh R Barrett, Scott M Turner, Ngoc-Anh Le, W Virgil Brown, Ernst J Schaefer
Small dense LDL (sdLDL) has been reported to be more atherogenic than large buoyant LDL (lbLDL). We examined the metabolism and protein composition of sdLDL and lbLDL in six subjects with combined hyperlipidemia on placebo and rosuvastatin 40 mg/day. ApoB-100 kinetics in triglyceride rich lipoproteins (TRL), lbLDL (density [d] 1.019-1.044 g/ml), and sdLDL (d 1.044-1.063 g/ml) were determined in the fed state using stable isotope tracers, mass spectrometry, and compartmental modeling. Compared with placebo, rosuvastatin decreased LDL cholesterol and apoB-100 levels in TRL, lbLDL, and sdLDL by significantly increasing the fractional catabolic rate of apoB-100 (TRL +45%; lbLDL +131%; sdLDL +97%), without a change in production...
April 9, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28389477/efad-transgenic-mice-as-a-human-apoe-relevant-preclinical-model-of-alzheimer-s-disease
#17
Leon M Tai, Deebika Balu, Evangelina Avila-Munoz, Laila Abdullah, Riya Thomas, Nicole Collins, Ana Carolina Valencia-Olvera, Mary Jo LaDu
Identified in 1993, APOE4 is the greatest genetic risk factor for sporadic Alzheimers disease (AD), increasing risk up to 12-fold compared to APOE3, with APOE2 decreasing AD risk. However, the functional effects of APOE4 on AD pathology remain unclear and, in some cases, controversial. In vivo progress to understand how the human (h)-APOE genotypes effect AD pathology has been limited by the lack of a tractable familial AD-transgenic (FAD-Tg) mouse model expressing h- rather than mouse (m)-APOE. The disparity between m- and h-apoE is relevant for virtually every AD-relevant pathway, including amyloid beta deposition and clearance, neuroinflammation, tau pathology, neural plasticity and cerebrovascular deficits...
April 7, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28381440/weekday-variation-in-triglyceride-concentrations-in-1-8-million-blood-samples
#18
Joern Jaskolowski, Christian Ritz, Anders Sjodin, Arne Astrup, Pal B Szecsi, Steen Stender, Mads F Hjorth
BACKGROUND: Triglyceride (TG) concentration is used as a marker of cardio-metabolic risk. However, diurnal and possibly weekday variation exists in TG concentrations. OBJECTIVE: To investigate weekday variation in TG concentrations among 1.8 million blood samples drawn between 2008 and 2015 from patients in the Capital region of Denmark. DESIGN: Plasma TG was extracted from a central clinical laboratory information system. Weekday variation was investigated by means of linear mixed models...
April 5, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28381441/role-of-lrp1-in-the-pathogenesis-of-alzheimer-s-disease-evidence-from-clinical-and-preclinical-studies
#19
Mitsuru Shinohara, Masaya Tachibana, Takahisa Kanekiyo, Guojun Bu
Among the low-density lipoprotein receptor (LDLR) family members, the roles of LDLR-related protein 1 (LRP1 or LRP) in the pathogenesis of Alzheimer's disease (AD), especially late-onset AD, have been the most studied by genetic, neuropathological and biomarker analyses (clinical studies) or cellular and animal model systems (preclinical studies) over the last 25 years. Although there are some conflicting reports, accumulating evidence from preclinical studies indicates that LRP1 not only regulates the metabolism of amyloid-β peptides (Aβ) in the brain and periphery, but also maintains brain homeostasis, impairment of which likely contributes to AD development in Aβ-independent manners...
April 4, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28377426/alterations-in-endo-lysosomal-function-induce-similar-hepatic-lipid-profiles-in-rodent-models-of-drug-induced-phospholipidosis-and-sandhoff-disease
#20
Emmanuelle Lecommandeur, David Baker, Timothy M Cox, Andrew W Nicholls, Julian L Griffin
Drug-induced phospholipidosis (DIPL) is characterised by an increase in the phospholipid content of the cell and the accumulation of drugs and lipids inside the lysosomes of affected tissues, including in the liver. While of uncertain pathological significance for patients, the condition remains a major impediment for the clinical development of new drugs. Human Sandhoff disease (SD) is caused by inherited defects of the β subunit of lysosomal β-hexosaminidases (Hex) A and B, leading to a large array of symptoms, including neurodegeneration and ultimately death by the age of four in its most common form...
April 4, 2017: Journal of Lipid Research
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