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Journal of Lipid Research

Shobini Jayaraman, Christian Haupt, Olga Gursky
Oxidative stress and inflammation, which involves a dramatic increase in serum amyloid A (SAA) levels, are critical in the development of atherosclerosis. Most SAA circulates on plasma HDL particles, altering their cardioprotective properties. SAA-enriched HDL have diminished anti-oxidant effects on LDL, which may contribute to atherogenesis. We determined combined effects of SAA enrichment and oxidation on biochemical changes in HDL. Normal human HDL were incubated with SAA, oxidized by various factors (Cu2+, myeloperoxidase, H2O2, OCl-), and analyzed for lipid and protein modifications and biophysical remodeling...
October 15, 2016: Journal of Lipid Research
Latisha Love-Gregory, Aldi T Kraja, Fiona Allum, Stella Aslibekyan, Åsa K Hedman, Yanan Duan, Ingrid B Borecki, Donna K Arnett, Mark I McCarthy, Panos Deloukas, Jose M Ordovas, Paul N Hopkins, Elin Grundberg, Nada A Abumrad
CD36 variants influence fasting lipids and risk of metabolic syndrome, but their impact on postprandial lipids, an independent risk factor for cardiovascular disease, is unclear. We determined effects of SNPs within a ~410-kb region encompassing CD36 and its proximal and distal promoters on chylomicron remnants (CM) and LDL particles at fasting, 3.5 and 6 hours following a high-fat meal (GOLDN study, n=1117). Five promoter variants associated with CM, four with delayed triglyceride clearance and five with LDL particle number...
October 11, 2016: Journal of Lipid Research
Cristina Cruz-Hernandez, Frederic Destaillats, Sagar K Thakkar, Laurence Goulet, Emma Wynn, Dominik Grathwohl, Claudia Roessle, Sara de Giorgi, Luc Tappy, Francesca Giuffrida, Vittorio Giusti
It was hypothesized that under induced lipid malabsorption/mal-digestion conditions, an enriched sn-1(3)-monoacylglycerol oil (MAG) may be a better carrier for n-3 LC-PUFA compared to triacylglycerol (TAG) from fish oil (FO). This monocentric, double blinded clinical trial examined the accretion of EPA (500 mg/d) and DHA (300 mg/d) when consumed as TAG or MAG, into the erythrocytes, plasma and chylomicrons of 45 obese (BMI ≥ 30 kg/m(2) and 40 kg/m(2)) volunteers who were and were not administered Orlistat, an inhibitor of pancreatic lipases...
October 5, 2016: Journal of Lipid Research
Matthew Peach, Ren Xu, Dan Fitzpatrick, Lisa Hamilton, Ransi Somaratne, Rob Scott, Scott M Wasserman, C Stephen Djedjos
The effects of cholesterol-lowering drugs, including those that reduce cholesterol synthesis (statins) and those that reduce cholesterol absorption (ezetimibe), on cholesterol absorption and synthesis are well understood. PCSK9 inhibitors are a novel class of cholesterol-lowering drugs that robustly reduce LDL-C, but little is known about their effects on cholesterol absorption and synthesis. We evaluated how treatment with evolocumab, a fully human monoclonal IgG2 antibody to PCSK9, affects markers of cholesterol synthesis and absorption by measuring these markers in patients from an evolocumab clinical trial...
October 5, 2016: Journal of Lipid Research
Kristian K Jensen, Marija Tadin-Strapps, Sheng-Ping Wang, James Hubert, Yanqing Kan, Yong Ma, David G McLaren, Stephen F Previs, Kithsiri B Herath, Ablatt Mahsut, Andy Liaw, Shubing Wang, Steven J Stout, CarolAnn Keohan, Gail Forrest, David Coelho, Satya Yendluri, Stephanie Williams, Martin Koser, Steven Bartz, Karen O Akinsanya, Shirly Pinto
SREBP cleavage-activating protein (SCAP) is a key protein in the regulation of lipid metabolism and a potential target for treatment of dyslipidemia. SCAP is required for activation of the transcription factors SREBP-1 and -2. SREBPs regulate the expression of genes involved in fatty acid and cholesterol biosynthesis, and LDL-C clearance through the regulation of LDLR and PCSK9 expression. To further test the potential of SCAP as a novel target for treatment of dyslipidemia, we used short interfering RNAs (siRNA) to inhibit hepatic SCAP expression and assess the effect on PCSK9, LDLR and lipids in mice and rhesus monkeys...
October 5, 2016: Journal of Lipid Research
Hisako Akiyama, Kazuki Nakajima, Yoshiyuki Itoh, Tomoko Sayano, Yoko Ohashi, Yoshiki Yamaguchi, Peter Greimel, Yoshio Hirabayashi
To date, sterylglucosides have been reported to be present in various fungi, plants, and animals. In bacteria, such as Helicobacter pylori, proton NMR spectral analysis of isolated cholesterylglucoside (GlcChol) demonstrated the presence of an α-glucosidic linkage. By contrast in animals, no detailed structural analysis of GlcChol has been reported, in part because animal-derived samples contain a high abundance of glucosylceramides/galactosylceramides, which exhibit highly similar chromatographic behavior to GlcChol...
October 3, 2016: Journal of Lipid Research
Petr Zacek, Michael Bukowski, Thad Rosenberger, Matthew Picklo
Phosphatidylcholine (PC) species in human plasma are used as biomarkers of disease. PC biomarkers are often limited by the inability to separate isobaric PCs. In this work, we developed a targeted shotgun approach for analysis of isobaric and isomeric PCs. This approach is comprised of two mass spectrometric (MS) methods: a precursor ion scanning of mass m/z 184 in positive mode (PIS m/z +184) and MS3 fragmentation in negative mode, both performed on the same instrument, a hybrid triple quadrupole ion-trap mass spectrometer...
September 29, 2016: Journal of Lipid Research
Borge G Nordestgaard, Anne Langsted
Human epidemiologic and genetic evidence using the Mendelian randomization approach in large-scale studies now strongly support that elevated lipoprotein(a) (Lp(a)) is a causal risk factor for cardiovascular disease, that is, for myocardial infarction, atherosclerotic stenosis, and aortic valve stenosis. The Mendelian randomization approach used to infer causality is generally not affected by confounding and reverse causation, the major problems of observational epidemiology. This approach is particularly valuable to study causality of Lp(a), as single genetic variants exist that explain 27-28% of all variation in plasma Lp(a)...
September 27, 2016: Journal of Lipid Research
Naoki Kobayashi, Masato Otsuka, Akihito Yamaguchi, Tsuyoshi Nishi
Sphingosine-1-phosphate (S1P) is present in the blood plasma and acts as a pivotal intercellular signal transmitter in the immune system by recruiting lymphocytes from the thymus and secondary lymphoid tissues. The plasma S1P concentration is maintained by the supply of S1P from erythrocytes. Previously, we showed that S1P release from erythrocytes is mediated by an ATP-dependent transporter. In this study, we attempted to establish a rapid and reliable method for measuring the S1P transport activity in erythrocytes by using a fluorescent S1P analog, 7-nitro-2-1,3-benzoxadiazol-4-yl (NBD)-labeled S1P...
September 21, 2016: Journal of Lipid Research
Wakako Takabe, Yasuomi Urano, Diep-Khanh Ho Vo, Kimiyuki Shibuya, Masaaki Tanno, Hiroaki Kitagishi, Toyoshi Fujimoto, Noriko Noguchi
24(S)-hydroxycholesterol (24S-OHC), which plays an important role in maintaining brain cholesterol homeostasis, has been shown to possess neurotoxicity. We have previously reported that 24S-OHC esterification by acyl-CoA:cholesterol acyltransferase 1 (ACAT1) and the resulting lipid droplet (LD) formation are responsible for 24S-OHC-induced cell death. In the present study, we investigate the functional roles of 24S-OHC esters and LD formation in 24S-OHC-induced cell death, and we identify four long-chain unsaturated fatty acids (oleic acid, linoleic acid, arachidonic acid, and docosahexaenoic acid) with which 24S-OHC is esterified in human neuroblastoma SH-SY5Y cells treated with 24S-OHC...
September 19, 2016: Journal of Lipid Research
Shogo Takahashi, Tatsuki Fukami, Yusuke Masuo, Chad N Brocker, Cen Xie, Kristopher W Krausz, C Roland Wolf, Colin J Henderson, Frank J Gonzalez
Bile acids are synthesized from cholesterol in the liver and subjected to multiple metabolic biotransformations in hepatocytes, including oxidation by cytochromes P450 (CYP)s and conjugation with taurine, glycine, glucuronic acid, and sulfate. Mice and rats can hydroxylate chenodeoxycholic acid (CDCA) at the 6-position to form α-muricholic acid (α-MCA), and ursodeoxycholic acid (UDCA) to form β-muricholic acid (-MCA). However, MCA is not formed in humans to any appreciable degree and the mechanism for this species difference is not known...
September 16, 2016: Journal of Lipid Research
Maria Podbielska, Zdzislaw M Szulc, Ewa Kurowska, Edward L Hogan, Jacek Bielawski, Alicja Bielawska, Narayan R Bhat
Th1 pro-inflammatory cytokines i.e., TNF-α and IFN-γ in combination are known to induce cell death in several cell types including oligodendrocytes but the mechanism of their synergistic cytotoxicity is unclear. Although ceramide (Cer) has been implicated in cytokine- and stress-induced cell death, its intracellular levels alone cannot explain cytokine synergy. We considered the possibility that Cer released as part of extracellular vesicles may contribute to cytokine-induced synergistic cell death. Using a human oligodendroglioma (HOG) cell line as a model, here we show that exosomes derived from TNF-α-treated donor cells, while being mildly toxic to fresh cultures (similar to individual cytokines), induce enhanced cell death when added to IFN-γ-primed target cultures in a fashion resembling the effect of cytokine combination...
September 13, 2016: Journal of Lipid Research
Zahir Hussain, Toru Uyama, Katsuhisa Kawai, Iffat Ara Sonia Rahman, Kazuhito Tsuboi, Nobukazu Araki, Natsuo Ueda
N-Acylphosphatidylethanolamines (NAPEs) are a class of glycerophospholipids, which are known as precursors for different bioactive N-acylethanolamines. We previously reported that phospholipase A/acyltransferase-1 (PLAAT-1), which was originally found in mammals as a tumor suppressor, catalyzes N-acylation of phosphatidylethanolamines to form NAPEs. However, recent online database suggested the presence of an uncharacterized isoform of PLAAT-1 with an extra sequence at N-terminus. In the present study, we examined the occurrence, intracellular localization and catalytic properties of this longer isoform as well as the original shorter isoform from humans and mice...
September 13, 2016: Journal of Lipid Research
Robin F Irvine
The diverse family of inositol lipids is now known to be central to many aspects of cell biology. The route from the first discovery of inositol to our present day knowledge of inositol lipids spans more than 150 years and is long and complex. This is a brief account of some of the most important stages along that route.
September 13, 2016: Journal of Lipid Research
Hang Su, Dan Zhou, Yuan-Xiang Pan, Xingguo Wang, Manabu T Nakamura
In mammals, because they share a single synthetic pathway, n-6/n-3 ratios of dietary PUFAs impact tissue arachidonic acid (ARA) and DHA content. Likewise, SNPs in the human fatty acid desaturase (FADS) gene cluster impact tissue ARA and DHA. Here we tested the feasibility of using heterozygous Fads2-null-mice (HET) as an animal model of human FADS polymorphisms. WT and HET mice were fed diets with linoleate/alpha-linolenate ratios of 1:1, 7:1 and 44:1 at 7% of diet. In WT liver, ARA and DHA in phospholipids varied >2x among dietary groups, reflecting precursor ratios...
September 9, 2016: Journal of Lipid Research
Alexina Orsoni, Patrice Thérond, Ricardo Tan, Philippe Giral, Paul Robillard, Anatol Kontush, Peter J Meikle, M John Chapman
AIMS: Atherogenic mixed dyslipidemia associates with oxidative stress and defective HDL antioxidative function in metabolic syndrome (MetS). The impact of statin treatment on the capacity of HDL to inactivate LDL-derived, redox-active phospholipid hydroperoxides (PCOOH) in MetS is indeterminate. METHODS AND RESULTS: Insulin-resistant, hypertriglyceridemic, hypertensive, obese males were treated with pitavastatin (4mg/day) for 180 days, resulting in marked reduction in plasma triglycerides (-41%) and LDL-C (-38%), with minor effects on HDL-cholesterol and apoAI...
August 31, 2016: Journal of Lipid Research
Fernando Martínez-Montañés, Museer A Lone, Fong-Fu Hsu, Roger Schneiter
Long-chain bases (LCBs) are the precursors to ceramide and sphingolipids in eukaryotic cells. They are formed by the action of serine palmitoyl-CoA transferase (SPT), a complex of integral membrane proteins located in the endoplasmic reticulum. SPT activity is negatively regulated by Orm proteins to prevent the toxic overaccumulation of LCBs. Here we show that overaccumulation of LCBs in yeast results in their conversion to a hitherto undescribed LCB derivative, a LCB vinyl ether. The LCB vinyl ether is predominantly formed from phytosphingosine (PHS) as revealed by conversion of odd chain length tracers C17-dihydrosphingosine (C17-DHS) and C17-PHS into the corresponding LCB vinyl ether derivative...
August 25, 2016: Journal of Lipid Research
Sarah Spiegel, Richard L Proia
No abstract text is available yet for this article.
August 17, 2016: Journal of Lipid Research
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No abstract text is available yet for this article.
October 2016: Journal of Lipid Research
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October 2016: Journal of Lipid Research
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