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Journal of Lipid Research

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https://www.readbyqxmd.com/read/29773713/a-thumbwheel-mechanism-for-apoa1-activation-of-lcat-activity-in-hdl
#1
Allison L Cooke, Jamie Morris, John T Melchior, Scott E Street, W Gray Jerome, Rong Huang, Andrew B Herr, Loren E Smith, Jere P Segrest, Alan T Remaley, Amy S Shah, Thomas B Thompson, W Sean Davidson
APOA1 is the most abundant protein in HDL. It modulates interactions that affect HDLs cardioprotective functions, in part via its activation of the enzyme LCAT. On nascent, discoidal HDL, APOA1 comprises 10 alpha-helical repeats arranged in an anti-parallel, stacked-ring structure that encapsulates a lipid bilayer. Previous chemical cross-linking studies suggested that these APOA1 rings can adopt at least two different orientations, or registries, with respect to each other; however, the functional impact of these structural changes is unknown...
May 17, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29769239/hypertriglyceridemia-and-cardiovascular-risk-a-cautionary-note-about-metabolic-confounding
#2
Allan D Sniderman, Patrick Couture, Seth B Martin, Jacqueline DeGraaf, Patrick R Lawler, William C Cromwell, John T Wilkins, George Thanassoulis
Triglycerides are the conventional tool to measure very low-density lipoproteins (VLDL) whereas low-density lipoprotein cholesterol (LDL-C) is the conventional tool to measure low-density lipoproteins (LDL). Multiple epidemiological studies, including a series of genetically based analyses, have demonstrated cardiovascular risk is related to triglycerides independently of LDL-C and this has led to a series of new therapeutic agents designed specifically to reduce plasma triglycerides. The triglyceride hypothesis posits that increased levels of triglycerides increase cardiovascular risk and decreasing plasma triglycerides decreases cardiovascular risk...
May 16, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29764924/normalized-neutral-lipid-quantitation-by-flow-cytometry
#3
Nathan E Wolins, Katerina N DeHaan, Vincenza Cifarelli, Angela K Stoeckman
Interest in measuring tissue lipids has increased as the link between fat laden tissues and metabolic disease has become obvious; however, linking disease to a specific cell type within a tissue has been hampered by methodological limitations. Flow cytometry has been used to assess relative lipid levels in cells. Unfortunately, its usefulness is limited, because comparisons between samples generated over several hours is problematic. We show that: 1) in lipophilic fluorophore stained cells, fluorescence intensity measured by flow cytometry reflects lipid levels; 2) this technique can be used to assess lipid levels in a mixed cell population; 3) normalizing to a control condition can decrease experiment-to-experiment variation; and 4) fluorescence intensity increases linearly with lipid levels...
May 15, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29764923/extracellular-vesicles-lipids-as-key-components-of-their-biogenesis-and-functions
#4
Michel Record, Sandrine Silvente-Poirot, Marc Poirot, Michael J O Wakelam
Intercellular communication has been known for decades to involve either direct contact between cells or to operate by spreading molecules such as cytokines, growth factors, or lipid mediators. Through the last decade we have begun to appreciate the increasing importance of intercellular communication mediated by extracellular vesicles released by viable cells either from plasma membrane shedding microvesicles, also named microparticles), or from an intracellular compartment (exosomes). Exosomes and microvesicles circulate in all biological fluids and can trigger biological responses at distance...
May 15, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29764922/introduction-to-thematic-review-series-on-extracellular-vesicles-a-focus-on-the-role-of-lipids
#5
Michel Record
An additional mechanism of intercellular communication has been unveiled by the characterization of extracellular vesicles, namely exosomes and microvesicles, released from viable cells and concentrating selected molecules from the parental cells and able to be addressed far from the emitting cells. Exosomes are naturally engineered nanovesicles, while microvesicles scale up to micron size. Among the numerous and diverse molecules they carry, these extracellular vesicles also contain a variety of lipid mediators...
May 15, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29739865/2-chlorofatty-acids-lipid-mediators-of-neutrophil-extracellular-trap-formation
#6
Elisa N D Palladino, Lalage A Katunga, Grant R Kolar, David A Ford
Neutrophils form neutrophil extracellular traps (NETs), which have been implicated in microcirculatory plugging. NET formation (NETosis) involves the fusion of granule and nuclear contents, which are then released in the extracellular space. Myeloperoxidase (MPO) plays a major role in NETosis leading to the dissociation of DNA from histones. During neutrophil activation, MPO is released and activated to convert hydrogen peroxide and chloride to hypochlorous acid (HOCl). HOCl targets plasmalogens leading to the production of the chlorinated lipids, 2-chlorofatty aldehyde (2-ClFALD) and 2-chlorofatty acid (2-ClFA)...
May 8, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29739864/genetic-dietary-and-sex-specific-regulation-of-hepatic-ceramides-and-relationship-between-hepatic-ceramides-and-insulin-resistance
#7
Frode Norheim, Thomas Bjellaas, Simon T Hui, Karthickeyan Chella Krishnan, Jakleen Lee, Sonul Gupta, Calvin Pan, Yehudit Hasin-Brumshtein, Brian W Parks, Daniel Li, Hai Bui, Marian Mosier, Yuping Wu, Adriana Huertas-Vazquez, Stanley W Hazen, Thomas E Gundersen, Margarete Mehrabian, Wilson Tang, Andrea L Hevener, Christian A Drevon, Aldons Jake Lusis
Elevated hepatic ceramides levels have been implicated in both insulin resistance (IR) and hepatic steatosis. To understand the factors contributing to hepatic ceramide levels in mice of both sexes, we have quantitated ceramides in a reference population of mice, the Hybrid Mouse Diversity Panel (HMDP) that has been previously characterized for a variety of metabolic syndrome traits. We observed significant positive correlations between Cer(d18:1/16:0) and IR/hepatic steatosis, consistent with previous findings, although the relationship broke down between sexes, as females were less insulin resistant but had higher Cer(d18:1/16:0) levels than males...
May 8, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29739863/effects-of-high-fat-diet-and-ampk-modulation-on-the-regulation-of-whole-body-lipid-metabolism
#8
Milena Schonke, Julie Massart, Juleen R Zierath
Metabolic flexibility, the capacity to adapt to fuel availability for energy production, is crucial for maintaining whole-body energy homeostasis. An inability to adequately promote fatty acid utilization is associated with lipid accumulation in peripheral tissues and contributes to the development of insulin resistance. In vivo assays to quantify whole-body lipid oxidation in mouse models of insulin resistance are lacking. We describe a method for assessing whole-body fatty acid oxidation in vivo , as well as tissue-specific lipid uptake in conscious mice...
May 8, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29739862/novel-gpihbp1-independent-pathway-for-clearance-of-plasma-tgs-in-angptl4-gpihbp1-mice
#9
Emily M Cushing, Kelli L Sylvers, Xun Chi, Shwetha K Shetty, Brandon Sj Davies
Mice lacking glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) are unable to traffic LPL to the vascular lumen. Thus, TG clearance is severely blunted, and mice are extremely hypertriglyceridemic. Paradoxically, mice lacking both GPIHBP1 and the LPL regulator angiopoietin-like 4 (ANGPTL4) are far less hypertriglyceridemic. We sought to determine the mechanism by which Angptl4 -/- Gpihbp1 -/- double knockout mice clear plasma triglycerides. We confirmed that, on a normal chow diet, plasma TG levels were lower in Angptl4 -/- Gpihbp1 -/- mice than in Gpihbp1 -/- mice; however, the difference disappeared with administration of a high-fat diet...
May 8, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29728460/aibp-inflammation-and-atherosclerosis
#10
Hainan Chen, Kai Yin
No abstract text is available yet for this article.
May 4, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29728459/abcg5-and-abcg8-more-than-a-defense-against-xenosterols
#11
Shailendra B Patel, Gregory Graf, Ryan Temel
The elucidation of the molecular basis of the rare disease Sitosterolemia has revolutionized our mechanistic understanding of how dietary sterols are excreted and how cholesterol is eliminated from the body. Two proteins ABCG5 and ABCG8, encoded by the Sitosterolemia locus, work as obligate dimers to pump sterols out of hepatocytes and enterocytes. ABCG5/ABCG8 are key in regulating whole-body sterol trafficking, by eliminating sterols via the biliary tree, as well as the intestinal tract. Importantly, these transporters keep xenosterols from accumulating in the body...
May 4, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29724783/-elovl4-and-fa2h-expression-during-rat-spermatogenesis-a-link-to-the-very-long-chain-pufa-typical-of-germ-cell-sphingolipids
#12
Florencia X Santiago Valtierra, Daniel A Penalva, Jessica M Luquez, Natalia E Furland, Claudia Vazquez, Juan G Reyes, Marta I Aveldano, Gerardo M Oresti
The sphingolipids (SL) of rodent spermatogenic cells (spermatocytes, spermatids) and spermatozoa contain nonhydroxylated and 2-hydroxylated versions of very-long-chain (C26 to C32) PUFA (n-V and h-V, respectively), not present in Sertoli cells. Here we investigated the expression of selected fatty acid elongases ( Elovl ), with a focus on Elovl4 , and a fatty acid 2-hydroxylase ( Fa2h ), in rat testes with postnatal development and germ cell differentiation. Along with Elovl5 and Elovl2 , Elovl4 was actively transcribed in the adult testis...
May 3, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29724782/identification-of-novel-lipid-modifications-and-inter-membrane-dynamics-in-corynebacterium-glutamicum-using-high-resolution-mass-spectrometry
#13
Stephan Klatt, Rajini Brammananth, Sean O'Callaghan, Konstantinos Andreas Kouremenos, Dedreia Tull, Paul K Crellin, Ross L Coppel, Malcolm J McConville
The complex cell envelopes of Corynebacterineae contribute to the virulence of pathogenic species (such as Mycobacterium tuberculosis and Corynebacterium diphtheriae) and capacity of non-pathogenic species (such as Corynebacterium glutamicum) to grow in diverse niches. The Corynebacterineae cell envelope comprises an asymmetric outer membrane, that overlays the arabinogalactan-peptidoglycan complex and the inner cell membrane. Dissection of the lipid composition of the inner and outer membrane fractions is important for understanding the biogenesis of this multi-laminate wall structure...
May 3, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29724781/identification-of-an-acid-sphingomyelinase-ceramide-kinase-pathway-in-the-regulation-of-the-chemokine-ccl5
#14
Benjamin Newcomb, Cosima Rhein, Izolda Mileva, Rasheed Ahmad, Christopher J Clarke, Justin Snider, Lina M Obeid, Yusuf A Hannun
Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to produce the biologically active lipid ceramide. Previous studies have implicated ASM in the induction of the chemokine CCL5 in response to TNF-α, however, the lipid mediator of this effect was not established. In the present study, we identified a novel pathway connecting ASM and ceramide kinase (CERK). The results show that TNF-α induces the formation of ceramide 1-phosphate (C-1-P) in a CERK-dependent manner. Silencing of CERK blocks CCL5 production in response to TNF-α...
May 3, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29724780/widely-targeted-quantitative-lipidomics-methodology-by-supercritical-fluid-chromatography-coupled-with-fast-scanning-triple-quadrupole-mass-spectrometry
#15
Hiroaki Takeda, Yoshihiro Izumi, Masatomo Takahashi, Thanai Paxton, Shohei Tamura, Tomonari Koike, Ying Yu, Noriko Kato, Katsutoshi Nagase, Masashi Shiomi, Takeshi Bamba
Lipidomics, the mass spectrometry-based comprehensive analysis of lipids, has attracted attention as an analytical approach to provide novel insight into lipid metabolism and to search for biomarkers. However, an ideal method for both comprehensive and quantitative analysis of lipids has not been fully developed. Herein, we have proposed a practical methodology for widely-targeted quantitative lipidome analysis using supercritical fluid chromatography fast-scanning triple-quadrupole mass spectrometry (SFC/QqQMS) and theoretically calculated a comprehensive lipid multiple reaction monitoring (MRM) library...
May 3, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29724779/determinants-of-ph-profile-and-acyl-chain-selectivity-in-lysosomal-phospholipase-a2
#16
Vania Hinkovska-Galcheva, Robert J Kelly, Kelly A Manthei, Renee Bouley, Wenmin Yuan, Anna Schwendeman, John J G Tesmer, James A Shayman
Lysosomal phospholipase A2 (LPA2) is characterized by broad substrate recognition, peak activity in acidic pH, and the transacylation of lipophilic alcohols, especially N-acetyl-sphingosine. Prior structural analysis of LPA2 revealed the presence of an atypical acidic residue, Asp13, in the otherwise hydrophobic active site cleft. We hypothesized that Asp13 contributed to the pH profile and/or substrate preference of LPA2 for unsaturated acyl chains. To test this hypothesis, we substituted Asp13 for alanine, cysteine, or phenylalanine; then, we monitored the formation of 1-O-acyl-N-acetylsphingosine to measure the hydrolysis of sn-1 versus sn-2 acyl groups on a variety of glycerophospholipids...
May 3, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29720388/scavenger-receptor-b-type-1-expression-molecular-regulation-and-cholesterol-transport-function
#17
Wen-Jun Shen, Shailendra Asthana, Fredric B Kraemer, Salman Azhar
Cholesterol is required for maintenance of plasma membrane fluidity and integrity and for many cellular functions. Cellular cholesterol can be obtained from lipoproteins in a selective pathway of HDL-cholesteryl ester (CE) uptake without parallel apolipoprotein uptake. Scavenger receptor B type 1 (SR-B1) is a cell surface HDL receptor that mediates HDL-CE uptake. It is most abundantly expressed in liver, where it provides cholesterol for bile acid synthesis, and in steroidogenic tissues, where it delivers cholesterol needed for storage or steroidogenesis in rodents...
May 2, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29716960/abnormal-liver-phosphatidylcholine-synthesis-revealed-in-patients-with-acute-respiratory-distress-syndrome
#18
Ahilanandan Dushianthan, Rebecca Cusack, Michael P W Grocott, Anthony D Postle
Acute respiratory distress syndrome (ARDS) is associated with a severe pro-inflammatory response; although decreased plasma cholesterol concentration has been linked to systemic inflammation, any association of phospholipid metabolic pathways with ARDS has not been characterized. Plasma phosphatidylcholine (PC), the major phospholipid of circulating lipoproteins, is synthesized in human liver by two biologically diverse pathways: the CDP:choline and phosphatidylethanolamine-N-methyltransferase (PEMT) pathways...
May 1, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29716959/the-phospholipase-a2-activity-of-peroxiredoxin-6
#19
Aron B Fisher
Peroxiredoxin 6 (Prdx6) is a Ca2+-independent intracellular phospholipase A2 (called aiPLA2) that is localized to cytosol and acidic organelles (lysosomes and lysosomal-related organelles). Activity is minimal at cytosolic pH but is increased significantly at acidic pH, in the presence of oxidized phospholipid substrate, with protein oxidation, and with enzyme phosphorylation; maximal activity with phosphorylated aiPLA2 is ~2 μmol/min/mg protein. Prdx6 is a ″moonlighting″ protein that also expresses peroxidase and lysophosphatidylcholine acyl transferase activities...
May 1, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29678960/toxoplasma-gondii-acetyl-coa-synthetase-is-involved-in-fatty-acid-elongation-of-long-fatty-acid-chains-during-tachyzoite-life-stages
#20
David Dubois, Stella Fernandes, Souad Amiar, Sheena Dass, Nicholas J Katris, Cyrille Y Botte, Yoshiki Yamaryo-Botte
Apicomplexan parasites are pathogens responsible for major human diseases such as toxoplasmosis caused by Toxoplasma gondii and malaria caused by Plasmodium spp.. Throughout their intracellular division cycle, the parasites require vast and specific amounts of lipids to divide and survive. This demand for lipids relies on a fine balance between de novo synthesized lipids and scavenged lipids from the host. Acetyl-CoA is a major and central precursor for many metabolic pathways especially for lipid biosynthesis...
April 20, 2018: Journal of Lipid Research
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