The Journal of Lipid Research
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1303 records returned
Persistence of an atherogenic lipid profile after treatment of acute infection with brucella [Patient-Oriented and Epidemiological Research]
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Serum lipid changes during infection may be associated with atherogenesis. No data are available on the effect of Brucellosis on lipids. Lipid parameters were determined in 28 patients with Brucellosis on admission and 4 months following treatment and were compared with 24 matched controls. Fasting levels of total cholesterol (TC), HDL-cholesterol (HDL-C), triglycerides, apolipoproteins (Apo) A, B, E CII, and CIII, and oxidized LDL (oxLDL) were measured. Activities of serum cholesterol ester transfer protein (CETP), paraoxonase 1 (PON1), and lipoprotein-associated phospholipase A2 (Lp-PLA2) and levels of cytokines [interle...
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Apostolou, F., Gazi, I. F., Kostoula, A., Tellis, C. C., Tselepis, A. D., Elisaf, M., Liberopoulos, E. N. Tags: Patient-Oriented and Epidemiological Research Source Type: journals
Chronic kidney disease delays VLDL-apoB-100 particle catabolism: potential role of apolipoprotein C-III [Patient-Oriented and Epidemiological Research]Email this article to a colleague.
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To determine the relative contribution of obesity and/or insulin resistance (IR) in the development of dyslipidemia in chronic kidney disease (CKD), we investigated the transport of apolipoprotein (apo) B-100 in nonobese, nondiabetic, nonnephrotic CKD subjects and healthy controls (HC). We determined total VLDL, VLDL1, VLDL2, intermediate density lipoprotein (IDL), and LDL-apoB-100 using intravenous D3-leucine, GC-MS, and multicompartmental modeling. Plasma apoC-III and apoB-48 were immunoassayed. In this case control study, we report higher plasma triglyceride, IDL-, VLDL-, VLDL1-, and VLDL2-apoB-100 concentrations in CKD...
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Chan, D. T., Dogra, G. K., Irish, A. B., Ooi, E. M., Barrett, P. H., Chan, D. C., Watts, G. F. Tags: Patient-Oriented and Epidemiological Research Source Type: journals
Esterase 22 and beta-glucuronidase hydrolyze retinoids in mouse liver [Research Articles]Email this article to a colleague.
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In conclusion, our observations implicate that both Es22 and Gus play a role in liver retinoid metabolism. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Schreiber, R., Taschler, U., Wolinski, H., Seper, A., Tamegger, S. N., Graf, M., Kohlwein, S. D., Haemmerle, G., Zimmermann, R., Zechner, R., Lass, A. Tags: Research Articles Source Type: journals
A novel role for fatty acid transport protein 1 in the regulation of tricarboxylic acid cycle and mitochondrial function in 3T3-L1 adipocytes [Research Articles]Email this article to a colleague.
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Fatty acid transport proteins (FATPs) are integral membrane acyl-CoA synthetases implicated in adipocyte fatty acid influx and esterification. Whereas some FATP1 translocates to the plasma membrane in response to insulin, the majority of FATP1 remains within intracellular structures and bioinformatic and immunofluorescence analysis of FATP1 suggests the protein primarily resides in the mitochondrion. To evaluate potential roles for FATP1 in mitochondrial metabolism, we used a proteomic approach following immunoprecipitation of endogenous FATP1 from 3T3-L1 adipocytes and identified mitochondrial 2-oxoglutarate dehydrogenase...
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Wiczer, B. M., Bernlohr, D. A. Tags: Research Articles Source Type: journals
The chemical chaperone 4-phenylbutyrate inhibits adipogenesis by modulating the unfolded protein response [Research Articles]Email this article to a colleague.
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Recent studies have shown a link between obesity and endoplasmic reticulum (ER) stress. Perturbations in ER homeostasis cause ER stress and activation of the unfolded protein response (UPR). Adipocyte differentiation contributes to weight gain, and we have shown that markers of ER stress/UPR activation, including GRP78, phospho-eIF2, and spliced XBP1, are upregulated during adipogenesis. Given these findings, the objective of this study was to determine whether attenuation of UPR activation by the chemical chaperone 4-phenylbutyrate (4-PBA) inhibits adipogenesis. Exposure of 3T3-L1 preadipocytes to 4-PBA in the presence of...
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Basseri, S., Lhotak, S., Sharma, A. M., Austin, R. C. Tags: Research Articles Source Type: journals
Human tear film and meibum. Very long chain wax esters and (O-acyl)-omega-hydroxy fatty acids of meibum [Research Articles]Email this article to a colleague.
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Human meibum was targetly analyzed for the presence of intact wax esters (WEs) and related compounds by means of reverse-phase HPLC in combination with ion trap mass spectrometry. The major detected WEs were based on C18:n (n = 1–4) unsaturated FAs ranking in the following order of abundance: C18:1>C18:2>C18:3>C18:4. The major fatty alcohols (FAls) found in WE were of saturated nature and varied from C18:0 to C28:0. The three most abundant species were C18:1-FA esters of C24:0, C25:0, and C26:0-FAl. Typically, a major compound based on C18:1-FA and a saturated FAl was accompanied by a few related compounds b...
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Butovich, I. A., Wojtowicz, J. C., Molai, M. Tags: Research Articles Source Type: journals
Whole-body synthesis secretion of docosahexaenoic acid from circulating eicosapentaenoic acid in unanesthetized rats [Research Articles]Email this article to a colleague.
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Dietary docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) are considered important for maintaining normal heart and brain function, but little EPA is found in brain, and EPA cannot be elongated to DHA in rat heart due to the absence of elongase-2. Ingested EPA may have to be converted in the liver to DHA for it to be fully effective in brain and heart, but the rate of conversion is not agreed on. This rate was determined in male adult rats fed a standard n-3 PUFA, containing diet by infusing unesterified albumin-bound [U-13C]EPA intravenously for 2 h and measuring esterified [13C]labeled PUFAs in...
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Gao, F., Kiesewetter, D., Chang, L., Ma, K., Rapoport, S. I., Igarashi, M. Tags: Research Articles Source Type: journals
Convergence of the 5-LOX and COX-2 pathways: heme-catalyzed cleavage of the 5S-HETE-derived di-endoperoxide into aldehyde fragments [Research Articles]Email this article to a colleague.
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Oxygenation of the 5-lipoxygenase product 5S-hydroxyeicosatetraenoic acid by cyclooxygenase-2 yields a bicyclic di-endoperoxide. The di-endoperoxide contains two peroxides spanning from carbons 9 to 11 and 8 to 12, and two hydroxyls at carbons 5 and 15 of arachidonic acid (Schneider C., et al. 2006. Convergent oxygenation of arachidonic acid by 5-lipoxygenase and cyclooxygenase-2. J. Am. Chem. Soc. 128: 720). Here, we report that treatment of the di-endoperoxide with hematin or ferrous chloride results in cleavage of both peroxide O-O bonds and of the bonds between the carbons that carry the peroxide groups, producing the ...
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Griesser, M., Boeglin, W. E., Suzuki, T., Schneider, C. Tags: Research Articles Source Type: journals
Molecular mechanism of recombinant liver fatty acid binding protein's antioxidant activity [Research Articles]Email this article to a colleague.
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We examined the antioxidant mechanism of a recombinant rat L-FABP in the presence of a hydrophilic (AAPH) or lipophilic (AMVN) free radical generator. Recombinant L-FABP amino acid sequence and its amino acid oxidative products following oxidation were identified by MALDI quadrupole time-of-flight MS after being digested by endoproteinase Glu-C. L-FABP was observed to have better antioxidative activity when free radicals were generated by the hydrophilic generator than by the lipophilic generator. Oxidative modification of L-FABP included up to five methionine oxidative peptide products with a total of ~80 Da mass shift co...
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Yan, J., Gong, Y., She, Y.-M., Wang, G., Roberts, M. S., Burczynski, F. J. Tags: Research Articles Source Type: journals
Analysis of pregnenolone and dehydroepiandrosterone in rodent brain: cholesterol autoxidation is the key [Research Articles]Email this article to a colleague.
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Pregnenolone (PREG) and dehydroepiandrosterone (DHEA), and their respective sulfated forms PREGS and DHEAS, were among the first steroids to be identified in rodent brain. However, unreliable steroid isolation and solvolysis procedures resulted in errors, particularly in the case of brain steroid sulfates analyzed by radioimmunology or GC-MS of liberated free steroids. By using a solid-phase extraction recycling/elution procedure, allowing the strict separation of sulfated, free, and fatty acid esters of PREG and DHEA, PREGS and DHEAS, unlike free PREG, were not detected in rat and mouse brain and plasma. Conversely, consi...
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Liere, P., Pianos, A., Eychenne, B., Cambourg, A., Bodin, K., Griffiths, W., Schumacher, M., Baulieu, E.-E., Sjovall, J. Tags: Research Articles Source Type: journals
GPIHBP1 stabilizes lipoprotein lipase and prevents its inhibition by angiopoietin-like 3 and angiopoietin-like 4 [Research Articles]Email this article to a colleague.
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Glycosylphosphatidylinositol-anchored HDL-binding protein (GPIHBP1) binds both LPL and chylomicrons, suggesting that GPIHBP1 is a platform for LPL-dependent processing of triglyceride (TG)-rich lipoproteins. Here, we investigated whether GPIHBP1 affects LPL activity in the absence and presence of LPL inhibitors angiopoietin-like (ANGPTL)3 and ANGPTL4. Like heparin, GPIHBP1 stabilized but did not activate LPL. ANGPTL4 potently inhibited nonstabilized LPL as well as heparin-stabilized LPL but not GPIHBP1-stabilized LPL. Like ANGPTL4, ANGPTL3 inhibited nonstabilized LPL but not GPIHBP1-stabilized LPL. ANGPTL3 also inhibited h...
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Sonnenburg, W. K., Yu, D., Lee, E-C., Xiong, W., Gololobov, G., Key, B., Gay, J., Wilganowski, N., Hu, Y., Zhao, S., Schneider, M., Ding, Z.-M., Zambrowicz, B. P., Landes, G., Powell, D. R., Desai, U. Tags: Research Articles Source Type: journals
Characterization of cis-9 trans-11 trans-15 C18:3 in milk fat by GC and covalent adduct chemical ionization tandem MS [Research Articles]Email this article to a colleague.
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The objective of this work was to identify a new isomer of octatridecenoic acid present in milk fat from ewes fed different sources of -linolenic acid. Structural characterization of this fatty acid was achieved by GC-MS. Analysis of dimethyloxazoline and picolinyl ester derivatives allowed for location of the double bond positions. Covalent adduct chemical ionization tandem mass spectrometry confirmed the positional structure 9-11-15, identical to RLnA, and helped to establish double bond geometry (cis-trans-trans). This new C18:3 isomer could be formed by isomerization of cis-15 bond of RLnA and subsequently converted by...
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Gomez-Cortes, P., Tyburczy, C., Brenna, J. T., Juarez, M., de la Fuente, M. A. Tags: Research Articles Source Type: journals
Improved cholesterol phenotype analysis by a model relating lipoprotein life cycle processes to particle size [Research Articles]Email this article to a colleague.
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Increased plasma cholesterol is a known risk factor for cardiovascular disease. Lipoprotein particles transport both cholesterol and triglycerides through the blood. It is thought that the size distribution of these particles codetermines cardiovascular disease risk. New types of measurements can determine the concentration of many lipoprotein size-classes but exactly how each small class relates to disease risk is difficult to clear up. Because relating physiological process status to disease risk seems promising, we propose investigating how lipoprotein production, lipolysis, and uptake processes depend on particle size....
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: van Schalkwijk, D. B., de Graaf, A. A., van Ommen, B., van Bochove, K., Rensen, P. C. N., Havekes, L. M., van de Pas, N. C. A., Hoefsloot, H. C. J., van der Greef, J., Freidig, A. P. Tags: Research Articles Source Type: journals
AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells [Research Articles]Email this article to a colleague.
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In this study, we found that Compound C treatment of MCF7 cells led to Bax redistribution from the cytoplasm to mitochondria and cell death. However, this effect does not involve AMPK. In addition, we found that treatment with this compound leads to an enhanced ceramide production. Analyses by quantitative PCR and ceramide synthase activity assay suggest that ceramide synthase 5 (LASS/CerS 5) is involved in Compound C-induced ceramide upregulation. Downregulation of LASS/CerS 5 was found to attenuate Compound C-mediated ceramide production, Bax redistribution, and cell death. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Jin, J., Mullen, T. D., Hou, Q., Bielawski, J., Bielawska, A., Zhang, X., Obeid, L. M., Hannun, Y. A., Hsu, Y.-T. Tags: Research Articles Source Type: journals
Docosahexaenoic acid reduces suppressive and migratory functions of CD4CD25 regulatory T-cells [Research Articles]Email this article to a colleague.
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In this study, we observed that docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, diminished, in a dose-dependent manner, the capacity of Treg cells to inhibit the CD4+CD25– effector T-cell proliferation. DHA not only reduced the migration of Treg cells toward chemokines but also downregulated the mRNA expression of CCR-4 and CXCR-4 in Treg cells. DHA also curtailed ERK1/2 and Akt phosphorylation and downregulated the Smad7 levels in these cells. Contradictorily, DHA upregulated the mRNA expression of Foxp3, CTLA-4, TGF-β, and IL-10; nonetheless, this fatty acid increased the expression of p27KIP1 m...
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Yessoufou, A., Ple, A., Moutairou, K., Hichami, A., Khan, N. A. Tags: Research Articles Source Type: journals
15(S)-Lipoxygenase-1 associates with neutral lipid droplets in macrophage foam cells: evidence of lipid droplet metabolism [Research Articles]Email this article to a colleague.
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15(S)-lipoxygenase-1 (15-LO-1) was present in the whole-cell homogenate of an acute human monocytic leukemia cell line (THP-1). Additionally, 15-LO-1 was detected on neutral lipid droplets isolated from THP-1 foam cells. To investigate if 15-LO-1 is active on lipid droplets, we used the mouse leukemic monocytic macrophage cell line (RAW 264.7), which are stably transfected with human 15-LO-1. The RAW 15-LO-1 cells were incubated with acetylated low density lipoprotein to generate foam cells. 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE], the major 15-LO-1 metabolite of arachidonic acid, was produced in the 15-LO-1 RAW bu...
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Weibel, G. L., Joshi, M. R., Wei, C., Bates, S. R., Blair, I. A., Rothblat, G. H. Tags: Research Articles Source Type: journals
LXR ligand lowers LDL cholesterol in primates, is lipid neutral in hamster, and reduces atherosclerosis in mouse [Research Articles]Email this article to a colleague.
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Liver X receptors (LXRs) are ligand-activated transcription factors that coordinate regulation of gene expression involved in several cellular functions but most notably cholesterol homeostasis encompassing cholesterol transport, catabolism, and absorption. WAY-252623 (LXR-623) is a highly selective and orally bioavailable synthetic modulator of LXR, which demonstrated efficacy for reducing lesion progression in the murine LDLR–/– atherosclerosis model with no associated increase in hepatic lipogenesis either in this model or Syrian hamsters. In nonhuman primates with normal lipid levels, WAY-252623 significant...
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Quinet, E. M., Basso, M. D., Halpern, A. R., Yates, D. W., Steffan, R. J., Clerin, V., Resmini, C., Keith, J. C., Berrodin, T. J., Feingold, I., Zhong, W., Hartman, H. B., Evans, M. J., Gardell, S. J., DiBlasio-Smith, E., Mounts, W. M., LaVallie, E. R., W Tags: Research Articles Source Type: journals
Bile acid transporters [Thematic Reviews]Email this article to a colleague.
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This article will review our current understanding of the physiological role and regulation of these important carriers. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Dawson, P. A., Lan, T., Rao, A. Tags: Thematic Reviews Source Type: journals
Bringing retinoid metabolism into the 21st century [Commentary]Email this article to a colleague.
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(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: van Berkel, T. J. C. Tags: Commentary Source Type: journals
Stabilizing lipoprotein lipase [Commentary]Email this article to a colleague.
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(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - November 13, 2009 Category: Lipidology Authors: Kersten, S., Bensadoun, A. Tags: Commentary Source Type: journals
ERRATA [Errata]Email this article to a colleague.
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(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Tags: Errata Source Type: journals
Metabolic precursors of surfactant disaturated-phosphatidylcholine in preterms with respiratory distress [Patient-Oriented and Epidemiological Research]Email this article to a colleague.
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Our objective was to study the metabolic precursors of surfactant disaturated-phosphatidylcholine (DSPC) in preterm infants with respiratory distress syndrome (RDS) on mechanical ventilation. We performed 46 DSPC kinetic studies in 23 preterms on fat-free parenteral nutrition and mechanical ventilation (birth weight = 1167 ± 451 g, gestational age = 28.5 ± 2.0 weeks). Eight infants received a simultaneous intravenous infusion of U13C-glucose and [16,16,16]2H-palmitate, eight infants received U13C-glucose and 2H2O, and seven received U13C-palmitate and 2H2O. Surfactant DSPC kinetics were calculated from the is...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Cogo, P. E., Ori, C., Simonato, M., Verlato, G., Isak, I., Hamvas, A., Carnielli, V. P. Tags: Patient-Oriented and Epidemiological Research Source Type: journals
Myocardial lipid accumulation in patients with pressure-overloaded heart and metabolic syndrome [Patient-Oriented and Epidemiological Research]Email this article to a colleague.
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We evaluated the role of sterol-regulatory element binding protein (SREBP)-1c/peroxisome proliferator activated receptor- (PPAR) pathway on heart lipotoxicity in patients with metabolic syndrome (MS) and aortic stenosis (AS). Echocardiographic parameters of heart function and structural alterations of LV specimens were studied in patients with (n = 56) and without (n = 61) MS undergoing aortic valve replacement. Tissues were stained with hematoxylin-eosin (H and E) and oil red O for evidence of intramyocyte lipid accumulation. The specimens were also analyzed with PCR, Western blot, and immunohistochemical analysis for SRE...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Marfella, R., Di Filippo, C., Portoghese, M., Barbieri, M., Ferraraccio, F., Siniscalchi, M., Cacciapuoti, F., Rossi, F., D'Amico, M., Paolisso, G. Tags: Patient-Oriented and Epidemiological Research Source Type: journals
Functional interaction of hormone-sensitive lipase and perilipin in lipolysis [Research Articles]Email this article to a colleague.
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Adipocyte lipolysis is controlled by complex interactions of lipases, cofactors, and structural proteins associated with lipid droplets. Perilipin (Plin) A is a major droplet-associated protein that functions as a scaffold, both suppressing basal and facilitating cAMP-dependent protein kinase (PKA)-stimulated lipolysis. Plin is required for the translocation of hormone-sensitive lipase (HSL) from the cytosol to lipid droplets upon stimulation. In these studies, we provide direct evidence for a physical interaction of HSL with Plin. By coexpressing HSL with truncation mutations of Plin, we demonstrate using coimmunoprecipit...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Shen, W.-J., Patel, S., Miyoshi, H., Greenberg, A. S., Kraemer, F. B. Tags: Research Articles Source Type: journals
Pharmacological inhibition of ABCA1 degradation increases HDL biogenesis and exhibits antiatherogenesis [Research Articles]Email this article to a colleague.
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We examined whether this approach could be a potential antiatherogenic treatment. Although probucol inhibits both the activity and degradation of ABCA1, its oxidized products, spiroquinone and diphenoquinone, reduce degradation of ABCA1 without inhibiting its activity or altering transcription of the ABCA1 gene. Accordingly, both compounds enhanced apolipoprotein A-I/ABCA1-dependent generation of HDL in vitro, and increased hepatic ABCA1 and plasma HDL without increasing antioxidant activity in plasma when given to rabbits. Both compounds also decreased vascular lipid deposition in cholesterol-fed rabbits. We therefore con...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Arakawa, R., Tsujita, M., Iwamoto, N., Ito-Ohsumi, C., Lu, R., Wu, C.-A., Shimizu, K., Aotsuka, T., Kanazawa, H., Abe-Dohmae, S., Yokoyama, S. Tags: Research Articles Source Type: journals
Spatial and temporal alterations of phospholipids determined by mass spectrometry during mouse embryo implantation [Research Articles]Email this article to a colleague.
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In this study, we used MALDI imaging mass spectrometry (IMS) technologies to characterize the spatial and temporal distribution of phospholipid species associated with mouse embryo implantation. Molecular images showing phospholipid distribution within implantation sites changed markedly between distinct cellular areas during days 4–8 of pregnancy. For example, by day 8, linoleate- and docosahexaenoate-containing phospholipids localized to regions destined to undergo cell death, whereas oleate-containing phospholipids localized to angiogenic regions. Arachidonate-containing phospholipids showed different segregation ...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Burnum, K. E., Cornett, D. S., Puolitaival, S. M., Milne, S. B., Myers, D. S., Tranguch, S., Brown, H. A., Dey, S. K., Caprioli, R. M. Tags: Research Articles Source Type: journals
Hepatic retinol secretion and storage are altered by dietary CLA: common and distinct actions of CLA c9,t11 and t10,c12 isomers [Research Articles]Email this article to a colleague.
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Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid obtained from ruminant products. Previous studies in rats and pigs showed that a dietary equimolar mixture of c9,t11 and t10,c12 CLA isomers induces changes in serum and tissue levels of retinoids (vitamin A derivatives). However, the mechanism(s) responsible for these actions remain(s) unexplored. Given the numerous crucial biological functions regulated by retinoids, it is key to establish whether the perturbations in retinoid metabolism induced by dietary CLA mediate some of the beneficial effects associated with intake of this fatty acid or, rather, have ad...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Ortiz, B., Wassef, L., Shabrova, E., Cordeddu, L., Banni, S., Quadro, L. Tags: Research Articles Source Type: journals
Sphingomyelin synthase SMS2 displays dual activity as ceramide phosphoethanolamine synthase [Research Articles]Email this article to a colleague.
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Sphingolipids are vital components of eukaryotic membranes involved in the regulation of cell growth, death, intracellular trafficking, and the barrier function of the plasma membrane (PM). While sphingomyelin (SM) is the major sphingolipid in mammals, previous studies indicate that mammalian cells also produce the SM analog ceramide phosphoethanolamine (CPE). Little is known about the biological role of CPE or the enzyme(s) responsible for CPE biosynthesis. SM production is mediated by the SM synthases SMS1 in the Golgi and SMS2 at the PM, while a closely related enzyme, SMSr, has an unknown biochemical function. We now d...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Ternes, P., Brouwers, J. F. H. M., van den Dikkenberg, J., Holthuis, J. C. M. Tags: Research Articles Source Type: journals
A quantitative assay measuring the function of lipase maturation factor 1 [Research Articles]Email this article to a colleague.
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In this report, we describe optimized conditions that ensure the detection of a complete range of Lmf1 function (full, partial, or complete loss of function) using LPL activity as the quantitative reporter. To illustrate the dynamic range of the assay, we tested several novel mutations in mouse Lmf1. Our results demonstrate the ability of the assay to detect and analyze Lmf1 mutations having a wide range of effects on Lmf1 function and protein expression. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Yin, F., Doolittle, M. H., Peterfy, M. Tags: Research Articles Source Type: journals
Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide [Research Articles]Email this article to a colleague.
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During screening of genes upregulated by lipopolysaccharide (LPS; endotoxin) treatment of bone marrow-derived mouse macrophages, it was unexpectedly found that cholesterol 25-hydroxylase (Ch25h) was strongly upregulated. Treatment of macrophages with 10 ng/ml of LPS for 2 h resulted in a 35-fold increase in the expression of Ch25h. In contrast, LPS treatment did not increase the expression of Cyp27a1 or Cyp7b1. The increased Ch25h expression was found to be independent of Myeloid differentiation protein 88 signaling but dependent on Toll-like receptor 4 signaling. LPS treatment of macrophages caused a 6- to 7-fold increase...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Diczfalusy, U., Olofsson, K. E., Carlsson, A.-M., Gong, M., Golenbock, D. T., Rooyackers, O., Flaring, U., Bjorkbacka, H. Tags: Research Articles Source Type: journals
Production and characterization of monoclonal anti-sphingosine-1-phosphate antibodies [Research Articles]Email this article to a colleague.
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This report describes the successful production and characterization of a murine monoclonal antibody, LT1002, directed against S1P, using novel immunization and screening methods applied to bioactive lipids. We also report the successful generation of LT1009, the humanized variant of LT1002, for potential clinical use. Both LT1002 and LT1009 have high affinity and specificity for S1P and do not cross-react with structurally related lipids. Using an in vitro bioassay, LT1002 and LT1009 were effective in blocking S1P-mediated release of the pro-angiogenic and prometastatic cytokine, interleukin-8, from human ovarian carcinom...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: O'Brien, N., Jones, S. T., Williams, D. G., Cunningham, H. B., Moreno, K., Visentin, B., Gentile, A., Vekich, J., Shestowsky, W., Hiraiwa, M., Matteo, R., Cavalli, A., Grotjahn, D., Grant, M., Hansen, G., Campbell, M.-A., Sabbadini, R. Tags: Research Articles Source Type: journals
Influence of class B scavenger receptors on cholesterol flux across the brush border membrane and intestinal absorption [Research Articles]Email this article to a colleague.
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To learn more about how the step of cholesterol uptake into the brush border membrane (BBM) of enterocytes influences overall cholesterol absorption, we measured cholesterol absorption 4 and 24 h after administration of an intragastric bolus of radioactive cholesterol in mice with scavenger receptor class B, type 1 (SR-BI) and/or cluster determinant 36 (CD36) deleted. The cholesterol absorption efficiency is unaltered by deletion of either one or both of the receptors. In vitro determinations of the cholesterol uptake specific activity of the BBM from the mice reveal that the scavenger receptors facilitate cholesterol upta...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Nguyen, D. V., Drover, V. A., Knopfel, M., Dhanasekaran, P., Hauser, H., Phillips, M. C. Tags: Research Articles Source Type: journals
Mechanism of inhibition defines CETP activity: a mathematical model for CETP in vitro [Research Articles]Email this article to a colleague.
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Because cholesteryl ester transfer protein (CETP) inhibition is a potential HDL-raising therapy, interest has been raised in the mechanisms and consequences of CETP activity. To explore these mechanisms and the dynamics of CETP in vitro, a mechanistic mathematical model was developed based upon the shuttle mechanism for lipid transfer. Model parameters were estimated from eight published experimental datasets, and the resulting model captures observed dynamics of CETP in vitro. Simulations suggest the shuttle mechanism yields behaviors consistent with experimental observations. Three key findings predicted from model simul...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Potter, L. K., Sprecher, D. L., Walker, M. C., Tobin, F. L. Tags: Research Articles Source Type: journals
Mice lacking Pctp /StarD2 exhibit increased adaptive thermogenesis and enlarged mitochondria in brown adipose tissue [Research Articles]Email this article to a colleague.
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Pctp–/– mice that lack phosphatidylcholine transfer protein (Pctp) exhibit a marked shift toward utilization of fatty acids for oxidative phosphorylation, suggesting that Pctp may regulate the entry of fatty acyl-CoAs into mitochondria. Here, we examined the influence of Pctp expression on the function and structure of brown adipose tissue (BAT), a mitochondrial-rich, oxidative tissue that mediates nonshivering thermogenesis. Consistent with increased thermogenesis, Pctp–/– mice exhibited higher core body temperatures than wild-type controls at room temperature. During a 24 h cold challenge, Pctp&nd...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Won Kang, H., Ribich, S., Kim, B. W., Hagen, S. J., Bianco, A. C., Cohen, D. E. Tags: Research Articles Source Type: journals
Signaling through cholesterol esterification: a new pathway for the cholecystokinin 2 receptor involved in cell growth and invasion [Research Articles]Email this article to a colleague.
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Several studies indicate that cholesterol esterification is deregulated in cancers. The present study aimed to characterize the role of cholesterol esterification in proliferation and invasion of two tumor cells expressing an activated cholecystokinin 2 receptor (CCK2R). A significant increase in cholesterol esterification and activity of Acyl-CoA:cholesterol acyltransferase (ACAT) was measured in tumor cells expressing a constitutively activated oncogenic mutant of the CCK2R (CCK2R-E151A cells) compared with nontumor cells expressing the wild-type CCK2R (CCK2R-WT cells). Inhibition of cholesteryl ester formation and ACAT ...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Paillasse, M. R., de Medina, P., Amouroux, G., Mhamdi, L., Poirot, M., Silvente-Poirot, S. Tags: Research Articles Source Type: journals
Fenofibrate and PBA prevent fatty acid-induced loss of adiponectin receptor and pAMPK in human hepatoma cells and in hepatitis C virus-induced steatosis [Research Articles]Email this article to a colleague.
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Adiponectin receptors play a key role in steatosis and inflammation; however, very little is known about regulation of adiponectin receptors in liver. Here, we examined the effects of palmitate loading, endoplasmic reticulum (ER) stress, and the hypolipidemic agent fenofibrate on adiponectin receptor R2 (AdipoR2) levels and AMP-activated protein kinase (AMPK) in human hepatoma Huh7 cells and in Huh.8 cells, a model of hepatitis C-induced steatosis. Palmitate treatment reduced AdipoR2 protein and basal AMPK phosphorylation in Huh7 cells. Fenofibrate treatment preserved AdipoR2 and phosphorylated AMPK (pAMPK) levels in palmi...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Rahman, S. M., Qadri, I., Janssen, R. C., Friedman, J. E. Tags: Research Articles Source Type: journals
Depletion of phosphatidylcholine affects endoplasmic reticulum morphology and protein traffic at the Golgi complex [Research Articles]Email this article to a colleague.
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The mutant Chinese hamster ovary cell line MT58 contains a thermosensitive mutation in CTP:phosphocholine cytidylyltransferase, the regulatory enzyme in the CDP-choline pathway. As a result, MT58 cells have a 50% decrease in their phosphatidylcholine (PC) level within 24 h when cultured at the nonpermissive temperature (40°C). This is due to a relative rapid breakdown of PC that is not compensated for by the inhibition of de novo PC synthesis. Despite this drastic decrease in cellular PC content, cells are viable and can proliferate by addition of lysophosphatidylcholine. By [3H]oleate labeling, we found that the FA mo...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Testerink, N., van der Sanden, M. H. M., Houweling, M., Helms, J. B., Vaandrager, A. B. Tags: Research Articles Source Type: journals
Attenuated suppression of the oxidative burst by cells dying in the presence of oxidized low density lipoprotein [Research Articles]Email this article to a colleague.
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Macrophages ingesting apoptotic cells attenuate inflammatory responses, such as reactive oxygen species (ROS) generation. In atherosclerosis, ongoing inflammation and accumulation of apoptotic/necrotic material are observed, suggesting defects of phagocytes in recognizing or responding to dying cells. Modified lipoproteins such as oxidized LDL (oxLDL) are known to promote inflammation and to interfere with apoptotic cell clearance. Here, we studied the impact of cells exposed to oxLDL on their ability to interfere with the oxidative burst in phagocytes. In contrast to apoptotic cells, cells dying in response to or in the p...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Namgaladze, D., Jennewein, C., Preiss, S., von Knethen, A., Brune, B. Tags: Research Articles Source Type: journals
Reducing CYP51 inhibits follicle-stimulating hormone induced resumption of mouse oocyte meiosis in vitro [Research Articles]Email this article to a colleague.
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Meiosis activating sterol, produced directly by lanosterol 14--demethylase (CYP51) during cholesterol biosynthesis, has been shown to promote the initiation of oocyte meiosis. However, the physiological significance of CYP51 action on oocyte meiosis in response to gonadotrophins’ induction remained to be further explored. Herein, we analyzed the role of CYP51 in gonadotrophin-induced in vitro oocyte maturation via RNA interference (RNAi). We showed that although both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) significantly induced meiotic resumption in follicle-enclosed oocytes (FEOs), the effect...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Wang, C., Xu, B., Zhou, B., Zhang, C., Yang, J., Ouyang, H., Ning, G., Zhang, M., Shen, J., Xia, G. Tags: Research Articles Source Type: journals
Gadolinium-containing phosphatidylserine liposomes for molecular imaging of atherosclerosis [Research Articles]Email this article to a colleague.
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Exteriorized phosphatidylserine (PS) residues in apoptotic cells trigger rapid phagocytosis by macrophage scavenger receptor pathways. Mimicking apoptosis with liposomes containing PS may represent an attractive approach for molecular imaging of atherosclerosis. We investigated the utility of paramagnetic gadolinium liposomes enriched with PS (Gd-PS) in imaging atherosclerotic plaque. Gd-PS-containing Gd-conjugated lipids, fluorescent rhodamine, and PS were prepared and characterized. Cellular uptake in RAW macrophages (fluorescent uptake of rhodamine) was studied on a fluorescence plate reader, while Gd-PS-induced alterat...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Maiseyeu, A., Mihai, G., Kampfrath, T., Simonetti, O. P., Sen, C. K., Roy, S., Rajagopalan, S., Parthasarathy, S. Tags: Research Articles Source Type: journals
Demonstrated and inferred metabolism associated with cytosolic lipid droplets [Thematic Reviews]Email this article to a colleague.
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Cytosolic lipid droplets were considered until recently to be rather inert particles of stored neutral lipid. Largely through proteomics is it now known that droplets are dynamic organelles and that they participate in several important metabolic reactions as well as trafficking and interorganellar communication. In this review, the role of droplets in metabolism in the yeast Saccharomyces cerevisiae, the fly Drosophila melanogaster, and several mammalian sources are discussed, particularly focusing on those reactions shared by these organisms. From proteomics and older work, it is clear that droplets are important for fat...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Goodman, J. M. Tags: Thematic Reviews Source Type: journals
Bile acids: the role of peroxisomes [Thematic Reviews]Email this article to a colleague.
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It is well established that peroxisomes play a crucial role in de novo bile acid synthesis. Studies in patients with a peroxisomal disorder have been indispensable for the elucidation of the precise role of peroxisomes. Several peroxisomal disorders are associated with distinct bile acid abnormalities and each disorder has a characteristic pattern of abnormal bile acids that accumulate, which is often used for diagnostic purposes. The patients have also been important for determining the pathophysiological consequences of defects in bile acid biosynthesis. In this review, we will discuss all the peroxisomal steps involved ...
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Ferdinandusse, S., Denis, S., Faust, P. L., Wanders, R. J. A. Tags: Thematic Reviews Source Type: journals
Myocardial lipid accumulation and lipotoxicity in heart failure [Commentary]Email this article to a colleague.
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(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - October 15, 2009 Category: Lipidology Authors: Schulze, P. C. Tags: Commentary Source Type: journals
A novel direct homogeneous assay for ATP citrate lyase [Methods]Email this article to a colleague.
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In this report, however, we describe a novel procedure to directly measure ACL enzyme activity. We first identified a convenient method to specifically detect [14C]acetyl-CoA without detecting [14C]citrate by MicroScint-O. Using this detection system, we devised a simple, direct, and homogeneous ACL assay in 384-well plate format that is suitable for high-throughput screening. The current assay consists of 1) incubation of ACL enzyme with [14C]citrate and other substrates/cofactors CoA, ATP, and Mg2+, 2) EDTA quench, 3) addition of MicroScint-O, the agent that specifically detects product [14C]acetyl-CoA, and 4) detection ...
Source: The Journal of Lipid Research - September 7, 2009 Category: Lipidology Authors: Ma, Z., Chu, C.-H., Cheng, D. Tags: Methods Source Type: journals
Highly sensitive quantification of serum malonate, a possible marker for de novo lipogenesis, by LC-ESI-MS/MS [Methods]Email this article to a colleague.
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We describe a new sensitive and specific method for the quantification of serum malonate (malonic acid, MA), which could be a new biomarker for de novo lipogenesis (fatty acid synthesis). This method is based upon a stable isotope-dilution technique using LC-MS/MS. MA from 50 µl of serum was derivatized into di-(1-methyl-3-piperidinyl)malonate (DMP-MA) and quantified by LC-MS/MS using the positive electrospray ionization mode. The detection limit of the DMP-MA was approximately 4.8 fmol (500 fg) (signal-to-noise ratio = 10), which was more than 100 times more sensitive compared with that of MA by LC-MS/MS using the n...
Source: The Journal of Lipid Research - September 7, 2009 Category: Lipidology Authors: Honda, A., Yamashita, K., Ikegami, T., Hara, T., Miyazaki, T., Hirayama, T., Numazawa, M., Matsuzaki, Y. Tags: Methods Source Type: journals
Changes in cholesterol absorption and cholesterol synthesis caused by ezetimibe and/or simvastatin in men [Patient-Oriented and Epidemiological Research]Email this article to a colleague.
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This study evaluates changes in cholesterol balance in hypercholesterolemic subjects following treatment with an inhibitor of cholesterol absorption or cholesterol synthesis or coadministration of both agents. This was a randomized, double blind, placebo-controlled, four-period crossover study to evaluate the effects of coadministering 10 mg ezetimibe with 20 mg simvastatin (ezetimibe/simvastatin) on cholesterol absorption and synthesis relative to either drug alone or placebo in 41 subjects. Each treatment period lasted 7 weeks. Ezetimibe and ezetimibe/simvastatin decreased fractional cholesterol absorption by 65% and 59%...
Source: The Journal of Lipid Research - September 7, 2009 Category: Lipidology Authors: Sudhop, T., Reber, M., Tribble, D., Sapre, A., Taggart, W., Gibbons, P., Musliner, T., von Bergmann, K., Lutjohann, D. Tags: Patient-Oriented and Epidemiological Research Source Type: journals
A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity [Patient-Oriented and Epidemiological Research]Email this article to a colleague.
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We explored the role of the adiponutrin (PNPLA3) nonsynonymous-rs738409 single nucleotide polymorphism (SNP) in genetic susceptibility to nonalcoholic fatty liver disease (NAFLD) and whether this SNP contributes to the severity of histological disease. Two hundred sixty-six individuals were evaluated in a case-control association study, which included 172 patients with features of NAFLD and 94 control subjects. The rs738409 G allele was significantly associated with NAFLD (P < 0.001; OR 2.8 95%, CI 1.5–5.2), independent of age, sex, body mass index (BMI), and Homeostasis Model Assessment (HOMA) index. When we test...
Source: The Journal of Lipid Research - September 7, 2009 Category: Lipidology Authors: Sookoian, S., Castano, G. O., Burgueno, A. L., Gianotti, T. F., Rosselli, M. S., Pirola, C. J. Tags: Patient-Oriented and Epidemiological Research Source Type: journals
Regulation of primary cilia formation by ceramide [Research Articles]Email this article to a colleague.
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The primary cilium is an important sensory organelle, the regulation of which is not fully understood. We found that in polarized Madin-Darby Canine Kidney cells, the sphingolipid ceramide is specifically distributed to a cis-Golgi compartment at the base of the primary cilium. This compartment immunostained for the centrosome marker -tubulin, the Rho type GTPase cell division cycle 42 (Cdc42), and atypical protein kinase C/ (aPKC), a kinase activated by ceramide and associated with a polarity protein complex consisting of partitioning defective (Par)6 and Cdc42. Inhibition of ceramide biosynthesis with Fumonisin B1 preven...
Source: The Journal of Lipid Research - September 7, 2009 Category: Lipidology Authors: Wang, G., Krishnamurthy, K., Bieberich, E. Tags: Research Articles Source Type: journals
Differential effects of simvastatin and pravastatin on expression of Alzheimer's disease-related genes in human astrocytes and neuronal cells [Research Articles]Email this article to a colleague.
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Inhibitors of HMG-CoA reductase (statins) are widely used medications for reduction of cholesterol levels. Statin use significantly reduces risk of cardiovascular disease but has also been associated with lower risk of other diseases and conditions, including dementia. However, some reports suggest that statins also have detrimental effects on the brain. We provide evidence that simvastatin and pravastatin have significantly different effects on expression of genes related to neurodegeneration in astrocytes and neuroblastoma (SK-N-SH) cells in culture. Simvastatin significantly reduced expression of ABCA1 in astrocytes and...
Source: The Journal of Lipid Research - September 7, 2009 Category: Lipidology Authors: Dong, W., Vuletic, S., Albers, J. J. Tags: Research Articles Source Type: journals
Four additional mouse crosses improve the lipid QTL landscape and identify Lipg as a QTL gene [Research Articles]Email this article to a colleague.
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To identify genes controlling plasma HDL and triglyceride levels, quantitative trait locus (QTL) analysis was performed in one backcross, (NZO/H1Lt x NON/LtJ) x NON/LtJ, and three intercrosses, C57BL/6J x DBA/2J, C57BL/6J x C3H/HeJ, and NZB/B1NJ x NZW/LacJ. HDL concentrations were affected by 25 QTL distributed on most chromosomes (Chrs); those on Chrs 1, 8, 12, and 16 were newly identified, and the remainder were replications of previously identified QTL. Triglyceride concentrations were controlled by nine loci; those on Chrs 1, 2, 3, 7, 16, and 18 were newly identified QTL, and the remainder were replications. Combining ...
Source: The Journal of Lipid Research - September 7, 2009 Category: Lipidology Authors: Su, Z., Ishimori, N., Chen, Y., Leiter, E. H., Churchill, G. A., Paigen, B., Stylianou, I. M. Tags: Research Articles Source Type: journals
