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Journal of Lipid Research

Olivia Tort, Tuixent Escriba, Lander Egana-Gorrono, Elisa de Lazzari, Montserrat Cofan, Emma Fernandez, Jose M Gatell, Esteban Martinez, Felipe Garcia, Mireia Arnedo
BACKGROUND: Cholesterol efflux (CE) capacity has been inversely associated with atherosclerosis and may provide an insight on inflammation occurring in HIV-individuals. We address this, by studying CE in HIV-patients at different stages of HIV-disease progression. METHODS: In this cross-sectional study CE from ApoB-depleted plasma, lipids levels, viral load (VL), CD4+/CD8+T-cell, high-sensitive-C-reactive protein (hsCRP) and lipoprotein(a) were evaluated in untreated HIV-patients (UHIV; n=43), elite controllers (EC; n=8), HIV-exposed seronegative (HESN; n=32) and healthy control (HC; n=14)...
September 13, 2018: Journal of Lipid Research
Maris A Cinelli, Jun Yang, Amy Scharmen, Joey Woodman, Lalitha M Karchalla, Kin Sing Stephen Lee
Epoxy PUFAs are endogenous cytochrome P450 metabolites of dietary PUFAs. Although these metabolites exert numerous biological effects, attempts to study their complex biology have been hampered by difficulty in obtaining the epoxides as pure regioisomers and enantiomers. To remedy this, we synthesized 19,20- and 16,17-epoxydocosapentaenoic acids (EDPs, two most abundant EDPs in vivo) by epoxidation of DHA with wild-type (WT) and the mutant (F87V) P450 enzyme BM3 from Bacillus megaterium. WT epoxidation yielded a 4:1 mixture of 19,20:16,17-EDP exclusively as (S,R) enantiomers...
September 12, 2018: Journal of Lipid Research
Mai H Philipsen, Sanna Samfors, Per Malmberg, Andrew G Ewing
Understanding fatty acid metabolism and lipid synthesis requires a lot of information about which fatty acids and lipids are formed within the cells. We focused on the use of deuterated tracers of α-linolenic acid and linoleic acid to determine the relative amounts of their converted polyunsaturated fatty acids (PUFAs) and specific phospholipids incorporated into cell plasma membranes. Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) was used to image and analyze lipids in model cell membranes with and without fatty acid treatment...
September 11, 2018: Journal of Lipid Research
Lydie Humbert, Dominique Rainteau, Noshine Tuvignon, Claude Wolf, Philippe Seksik, Rene Laugier, Frederic Carriere
Bile acid (BA) secretion and circulation in chronic pancreatitis (CP) patients with exocrine pancreatic insufficiency (EPI) were investigated by measuring simultaneously postprandial levels of individual BAs in duodenal contents and blood plasma using LC-MS/MS. CP patients and healthy volunteers (HV) were intubated with gastric and duodenal tubes prior to the administration of a test meal and continuous aspiration of duodenal contents. Pancreatic lipase outputs in CP patients were very low (0.7±0.2 mg) vs...
September 11, 2018: Journal of Lipid Research
Danielle E Dye, Mark A Bieniawski, Sarah C E Wright, Angela McCauley, Deirdre R Coombe, Carl J Mousley
Oxysterol-binding protein (OSBP) and its related proteins (ORPs) are a large, essential family of eukaryotic proteins that possess an array of cell activities. The founding member of this superfamily, OSBP, was first discovered through its ability to bind to cholesterol and its oxygenated derivatives. Subsequently, it was the predominant view that the core function of OSBP/ORPs was to facilitate the non-vesicular transport of sterols and other lipids at membrane contact sites (MCS). However, more recently it has been suggested that the OSBP/ORPs also act as phosphoinositide coupled lipid sensors at these sites, where they modulate organelle lipid composition and direct the assembly of effector protein complexes...
September 10, 2018: Journal of Lipid Research
Jamal M Bryant, Raymond D Blind
Phosphoinositide membrane signaling is critical for normal physiology, playing well-known roles in diverse human pathologies. The basic mechanisms governing phosphoinositide signaling within the nucleus, however, have remained deeply enigmatic owing to their presence outside the nuclear membranes. Over 40% of nuclear phosphoinositides can exist in this non-membrane state, held soluble in the nucleoplasm by nuclear proteins that remain largely unidentified. Recently, two nuclear proteins responsible for solubilizing phosphoinositides were identified - steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homolog-1 (LRH-1, NR5A2) - along with two enzymes that directly remodel these phosphoinositide/protein complexes - phosphatase and tensin homolog (PTEN, MMAC) and inositol polyphosphate multikinase (IPMK, ipk2)...
September 10, 2018: Journal of Lipid Research
Gattadahalli M Anantharamaiah, David W Garber, Dennis Goldberg, Eric Morrel, Geeta Datta, Mayakonda Palgunachari, Thomas C Register, Susan E Appt, C Roger White
Ac-hE18A-NH2 is a dual-domain apoE mimetic peptide that possesses the putative receptor binding domain from apoE (LRKLRKRLLR, denoted hE, residues 141 to 150) covalently attached to lipid-associating peptide 18A. Like apoE, Ac-hE18A-NH2 reduces plasma cholesterol in animal models and exhibits anti-inflammatory properties independent of its cholesterol-reducing effect. Ac-hE18A-NH2 has already undergone phase I clinical trials as a lipid-lowering agent. To explore the therapeutic potential more, we designed and synthesized new analogs by linking ɑ-aminohexanoic acid, octanoic acid, or myristic acid to LRRLRRRLLR-18A-NH2 ([R]hE18A-NH2) and examined the cholesterol-lowering potency in animals...
September 10, 2018: Journal of Lipid Research
Ana Raquel Ramos, Somadri Ghosh, Christophe Erneux
Phosphoinositides (PIs) are recognized as major signaling molecules in many different functions of eukaryotic cells. PIs can be dephosphorylated by multiple phosphatase activities at the 5-, 4- and 3- positions. Human PI 5-phosphatases belong to a family of 10 members. Except for INPP5A, they all catalyze the dephosphorylation of PI(4,5)P2 and/or PI(3,4,5)P3 at the 5- position. PI 5-phosphatases thus directly control the levels of PI(3,4,5)P3 and also participate in fine-tuning regulatory mechanisms of PI(3,4)P2 and PI(4,5)P2...
September 7, 2018: Journal of Lipid Research
Srividya Velagapudi, Peter Schraml, Mustafa Yalcinkaya, Hella Anna Bolck, Lucia Rohrer, Holger Moch, Arnold von Eckardstein
Clear cell renal cell carcinomas (ccRCC) are characterized by inactivation of von Hippel-Lindau (VHL) gene and intracellular lipid accumulation by unknown pathomechanism. The immunochemical analysis of 356 RCCs revealed high abundance of apolipoproteins apoA-I and apoB as well as scavenger receptor BI (SR-BI) in the clear cell RCC subtype. Given the characteristic loss of VHL function in ccRCC, we used VHL-defective and VHL-proficient cells to study the potential influence of VHL on lipoprotein uptake. VHL-defective patient-derived ccRCC cells and cell lines (786O and RCC4) showed enhanced uptake as well as less re-secretion and degradation of radio-iodinated high and low density lipoproteins (125I-HDL and 125I-LDL) compared to the VHL-proficient cells...
September 1, 2018: Journal of Lipid Research
Chad N Brocker, Daxesh P Patel, Thomas J Velenosi, Donghwan Kim, Tingting Yan, Jiang Yue, Guolin Li, Kristopher W Krausz, Frank J Gonzalez
PPARA, expressed in most oxidative tissues, is a major regulator of lipid homeostasis; hepatic PPARA plays a critical role during adaptive fasting response by promoting FA oxidation (FAO). To clarify whether extrahepatic PPARA activity can protect against lipid overload when hepatic PPARA is impaired, lipid accumulation was compared in wild-type (Ppara+/+), total body Ppara-null (Ppara-/-), and hepatocyte-specific Ppara-null (PparaΔHep) mice that were fasted for 24 hours. Histologic staining indicated reduced lipid accumulation in PparaΔHep versus Ppara-/- mice, and biochemical analyses revealed diminished medium- and long-chain FA accumulation in PparaΔHep mouse livers...
August 29, 2018: Journal of Lipid Research
Ruenn Chai Lai, Sai Kiang Lim
Therapeutic efficacy of the mesenchymal stromal cell (MSC), a multipotent progenitor cell, is attributed to small (50 to 200 nm) extracellular vesicles (EVs). The presence of a lipid membrane differentiates exosomes and EVs from other macromolecules. Analysis of this lipid membrane revealed three distinct small MSC EV subtypes each with a differential affinity for cholera toxin B chain (CTB), annexin V (AV), and shiga toxin B chain (ST) that binds GM1 ganglioside, phosphatidylserine, and globotriaosylceramide, respectively...
August 28, 2018: Journal of Lipid Research
Wataru Sakamoto, Nicolas Coant, Daniel Canals, Lina M Obeid, Yusuf A Hannun
Ceramidases hydrolyze ceramides into sphingosine and fatty acids, with sphingosine being further metabolized into sphingosine 1-phosphate (S1P); thus ceramidases control the levels of these bioactive sphingolipids in cells and tissues. Neutral ceramidase (nCDase) is highly expressed in colorectal tissues, and a recent report showed that nCDase activity is involved in Wnt/β-catenin signaling, and inhibition of nCDase decreases the development and progression of colorectal tumor growth. Here, in order to determine the action of nCDase in colorectal cancer cells, we focused on the subcellular localization and metabolic functions of this enzyme in HCT116 cells...
August 28, 2018: Journal of Lipid Research
Jihui Ren, Essa M Saied, Aaron Zhong, Justin Snider, Christian Ruiz, Christoph Arenz, Lina M Obeid, Geoffrey D Girnun, Yusuf A Hannun
Generation of most sphingolipids (SPLs) starts with condensation between serine and an activated long-chain fatty acid catalyzed by serine palmitoyltransferase (SPT). SPT can also use other amino acids to generate small quantities of noncanonical SPLs. The balance between serine-derived and noncanonical SPLs is pivotal; for example, hereditary sensory and autonomic neuropathy type I results from SPT mutations that cause abnormal accumulation of alanine-derived SPLs. The regulatory mechanism for SPT amino acid selectivity and the physiological functions of noncanonical SPLs are unknown...
August 28, 2018: Journal of Lipid Research
Jorge H Capdevila, John R Falck
The initial studies of the metabolism of arachidonic acid by the cytochrome P450 hemeproteins sought to: a) elucidate the roles for these enzymes in the metabolism of endogenous pools of the fatty acid, b) identify the P450 isoforms involved in arachidonic acid epoxidation and ω/ω-1 hydroxylation, and c) explore the biological activities of their metabolites. These early investigations provided a foundation for subsequent efforts to establish the physiological relevance of the arachidonic acid monooxygenase and its contributions to the pathophysiology of, for example, cancer, diabetes, hypertension, inflammation, nociception, and vascular disease...
August 28, 2018: Journal of Lipid Research
Vyala Hanumanthareddy Chaithra, Shancy Petsel Jacob, Chikkamenahalli Lakshminarayana Lakshmikanth, Mosale Seetharam Sumanth, Kandahalli Venkataranganayaka Abhilasha, Chu-Huang Chen, Anita Thyagarajan, Ravi P Sahu, Jeffery Bryant Travers, Thomas M McIntyre, Kempaiah Kemparaju, Gopal Kedithlu Marathe
Platelet-activating factor (alkyl-PAF) is a potent inflammatory mediator that exerts its actions via single PAF receptor (PAF-R). Cells that biosynthesize alkyl-PAF also make abundant amounts of the less potent PAF analog acyl-PAF, which competes for PAF-R. Both PAF species are degraded by plasma form of PAF acetylhydrolase (PAF-AH). We examined whether co-generated acyl-PAF protects alkyl-PAF from systemic degradation by acting as a sacrificial substrate to enhance inflammatory stimulation or if it acts as an inhibitor to dampen PAF-R signaling...
August 23, 2018: Journal of Lipid Research
Pallavi Mukherjee, Greg Hough, Arnab Chattopadhyay, Victor Grijalva, Ellen Ines O'Connor, David Meriwether, Alan Wagner, James M Ntambi, Mohamad Navab, Srinivasa T Reddy, Alan M Fogelman
After crossing floxed stearoyl co-A desaturase-1 (Scd1fl/fl) mice with ldlr-/- mice, and then Villin Cre (VilCre) mice, enterocyte Scd1 expression in Scd1fl/fl/ldlr-/-/VilCre mice was reduced 70%. On Western diet (WD), Scd1fl/fl/ldlr-/- mice gained more weight than Scd1fl/fl/ldlr-/-/VilCre mice (p<0.0023). On WD, jejunum levels of lysophosphatidylcholine (LysoPC) 18:1 and lysophosphatidic acid (LPA) 18:1 were significantly less in Scd1fl/fl/ldlr-/-/VilCre compared to Scd1fl/fl/ldlr-/- mice (p < 0.0004 and p < 0...
August 23, 2018: Journal of Lipid Research
Andrea E DeBarber, Limor Kalfon, Ayalla Fedida, Vered Fleisher Sheffer, Shani Ben Haroush, Natalia Chasnyk, Ephrat Shuster Biton, Hanna Mandel, Krystal Jeffries, Eric S Shinwell, Tzippora C Falik-Zaccai
Cerebrotendinous xanthomatosis (CTX) is a progressive metabolic leukodystrophy. Early identification and treatment from birth onward effectively provides a functional cure, but diagnosis is often delayed. We conducted a pilot study using a two-tier test for CTX to screen archived newborn dried bloodspots (DBS) or samples prospectively collected from a high-risk Israeli newborn population. All DBS samples were analyzed with flow injection-MS/MS (FIA-MS/MS), and 5% of samples were analyzed with LC-MS/MS. Consecutively collected samples were analyzed to identify CTX-causing founder genetic variants common among Druze and Moroccan Jewish populations...
August 22, 2018: Journal of Lipid Research
Rabia Asghar, Maria Chondronikola, Edgar L Dillon, William J Durham, Craig Porter, Zhanpin Wu, Maria Camacho-Hughes, Clark R Andersen, Heidi Spratt, Elena Volpi, Melinda Sheffield-Moore, Labros Sidossis, Robert R Wolfe, Nicola Abate, Demidmaa R Tuvdendorj
Intramyocellular triglyceride (imTG) in skeletal muscle plays a significant role in metabolic health, and an infusion of [13C16]-palmitate can be used to quantitate the in vivo fractional and absolute synthesis rates (FSR and ASR, respectively) of imTGs. However, the extramyocellular TG (emTG) pool, unless precisely excised, contaminates the imTG pool, diluting the imTG-bound tracer enrichment and leading to underestimation of FSR. Because of the difficulty of excising the emTGs precisely, it would be advantageous to be able to calculate the imTG synthesis rate without dissecting the emTGs from each sample...
August 21, 2018: Journal of Lipid Research
Bo Burla, Makoto Arita, Masanori Arita, Anne K Bendt, Amaury Cazenave-Gassiot, Edward A Dennis, Kim Ekroos, Xianlin Han, Kazutaka Ikeda, Gerhard Liebisch, Michelle K Lin, Tze Ping Loh, Peter J Meikle, Matej Orešič, Oswald Quehenberger, Andrej Shevchenko, Federico Torta, Michael J O Wakelam, Craig E Wheelock, Markus R Wenk
Human blood is a self-regenerating, lipid-rich biologic fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in lipid metabolism also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on mass spectrometry (MS) is an emerging tool in an array of clinical diagnostics and disease management...
August 16, 2018: Journal of Lipid Research
Jonghwa Lee, Neale D Ridgway
Intracellular lipid droplets (LDs) supply fatty acids for energy, membrane biogenesis, and lipoprotein secretion. The surface monolayer of LDs is composed of phospholipids, primarily phosphatidylcholine (PC), that stabilize the neutral lipid core of TG. To determine the relationship between PC synthesis and TG storage and secretion in chylomicrons, we used a model of intestinal-derived human epithelial colorectal adenocarcinoma (Caco2) cells with knockout of PCYT1A, which encodes the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase α (CCTα) in the CDP-choline pathway, that were treated with the fatty acid oleate...
August 16, 2018: Journal of Lipid Research
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