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Journal of Lipid Research

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https://www.readbyqxmd.com/read/28096191/allosteric-modulation-of-the-substrate-specificity-of-acyl-coa-wax-alcohol-acyltransferase-2-awat2
#1
Jason M Arne, Made Airanthi K Widjaja-Adhi, Taylor Hughes, Kevin W Huynh, Josie A Silvaroli, Sylwia Chelstowska, Vera Y Moiseenkova-Bell, Marcin Golczak
The esterification of alcohols with fatty acids is a universal mechanism to form inert storage forms of sterols, di- and triacylglycerols, and retinoids. In ocular tissues, formation of retinyl esters is an essential step in the enzymatic regeneration of the visual chromophore (11-cis-retinal). Acyl-CoA wax alcohol acyltransferase 2 (AWAT2), also known as multifunctional O-acyltransferase (MFAT), is an integral membrane enzyme with a broad substrate specificity that has been shown to preferentially esterify 11-cis-retinol and thus contribute to formation of readily available pool of cis retinoids in the eye...
January 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28082410/sphingomyelins-and-ceramides-with-very-long-chain-pufa-are-excluded-from-low-density-raft-like-domains-in-differentiating-spermatogenic-cells
#2
Florencia X Santiago Valtierra, Melina V Mateos, Marta I Aveldaño, Gerardo M Oresti
Rat spermatogenic cells contain sphingomyelins (SM) and ceramides (Cer) with very long-chain (VLC) PUFA, in nonhydroxylated (n-V) and 2-hydroxylated (h-V) forms. How these atypical species distribute among membrane fractions during differentiation was investigated here using a detergent-free procedure to isolate a small light, raft-like, low-density (L) fraction and a large heavy (H) fraction, mostly derived from the plasma membrane, of spermatocytes, round, and late spermatids. The L fraction contained cholesterol, glycerophospholipids and SM with the same saturated fatty acids in all three stages...
January 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28082409/unbound-free-fatty-acid-profiles-in-human-plasma-and-the-unexpected-absence-of-unbound-palmitoleate
#3
Andrew H Huber, Alan M Kleinfeld
We determined for the first time the profiles of the 9 most abundant unbound FFA (FFAu) in human plasma. Profiles were determined for a standard reference plasma of pooled healthy adults for which the Lipid Maps consortium had determined the total FFA profiles. Measurements were performed using twenty different acrylodan labeled fatty acid binding protein mutants (probes) which have complementary specificities for the 9 FFA that comprise more than 96% of long chain plasma FFA. The acrylodan fluorescence emission for each probe changes upon binding a FFAu...
January 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28073941/prognostic-roles-of-tetrahydroxy-bile-acids-in-infantile-intrahepatic-cholestasis
#4
Chee-Seng Lee, Akihiko Kimura, Jia-Feng Wu, Yen-Hsuan Ni, Hong-Yuan Hsu, Mei-Hwei Chang, Hiroshi Nittono, Huey-Ling Chen
Tetrahydroxy bile acids (THBAs) are hydrophilic and are present at minimal or undetectable levels in healthy human adults but are present at high levels in bile salt export pump (abcb11)-knockout mice. The roles of THBAs in human cholestatic diseases are unclear. We aimed to investigate the presence of THBAs in patients with infantile intrahepatic cholestasis and its correlation with outcome. Urinary bile acids were analysed by GC-MS. Data were compared between good (N=21) (disease-free before 1 year old) and poor prognosis groups (N=19)...
January 10, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28053186/intracardiac-injection-of-aav9-npc1-significantly-ameliorates-purkinje-cell-death-and-behavioral-abnormalities-in-mouse-niemann-pick-type-c-disease
#5
Chang Xie, Xue-Min Gong, Jie Luo, Bo-Liang Li, Bao-Liang Song
Niemann-Pick type C (NPC) disease is a fatal, inherited neurodegenerative disorder caused by loss-of-function mutations in the NPC1 or NPC2 gene. There is no effective way to treat NPC disease. In this study, we used adeno-associated virus (AAV) serotype 9 to deliver a functional NPC1 gene systemically into NPC1-/- mice at postnatal day 4 (P4). One single AAV9-NPC1 injection resulted in robust NPC1 expression in various tissues including the brain, heart and lung. Strikingly, AAV9-mediated NPC1 delivery significantly promoted Purkinje cell survival, restored locomotor activity and coordination, as well as increased the lifespan of NPC1-/- mice...
January 4, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28053185/macrophage-ltb4-drives-efficient-phagocytosis-of-borrelia-burgdorferi-via-blt1-or-blt2
#6
Yan Zhang, Rachel M Olson, Charles R Brown
Unresolved experimental Lyme arthritis in C3H 5-LOX-/- mice is associated with impaired macrophage phag-ocytosis of Borrelia burgdorferi. In the present study, we further investigated the effects of the 5-LOX metabolite, LTB4, on phagocytosis of B. burgdorferi. Bone marrow-derived macrophages (BMDM) from 5-LOX-/- mice were defective in the uptake and killing of B. burgdorferi from the earliest stages of spirochete internali-zation. BMDM from mice deficient for the LTB4 high-affinity receptor (BLT1-/-) were also unable to efficiently phagocytose B...
January 4, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28049656/hdl-efflux-capacity-hdl-particle-size-and-high-risk-carotid-atherosclerosis-in-a-cohort-of-asymptomatic-older-adults-the-chicago-healthy-aging-study
#7
R Kannan Mutharasan, C Shad Thaxton, Jarett Berry, Martha L Daviglus, Chun Yuan, Jie Sun, Colby Ayers, Donald M Lloyd-Jones, John T Wilkins
HDL efflux capacity and particle size are associated with atherosclerotic cardiovascular disease events in middle age, however it is unclear if these associations are present at older ages. We sampled 402 Chicago Healthy Aging Study participants who underwent carotid MR assessment for lipid rich necrotic core plaque (LRNC). We measured HDL particle size, HDL particle number, and HDL efflux capacity. We quantified the associations between HDL particle size and HDL efflux and the presence of LRNC and HDL particle number, and HDL efflux capacity using adjusted linear and logistic regression models...
January 3, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28039331/hepatic-deletion-of-x-box-binding-protein-1-impairs-bile-acid-metabolism-in-mice
#8
Xiaoying Liu, Anne S Henkel, Brian E LeCuyer, Susan C Hubchak, Matthew J Schipma, Eric Zhang, Richard M Green
The unfolded protein response (UPR) is an adaptive response to endoplasmic reticulum stress and the inositol-requiring enzyme 1α/X-box binding protein 1 (IRE1α/XBP1) pathway of the UPR is important in lipid metabolism. However, its role in bile acid metabolism remains unknown. We demonstrate that liver-specific Xbp1 knockout (LS-Xbp1(-/-)) mice had a 45% reduction in total bile acid pool. LS-Xbp1(-/-) mice had lower serum 7α-hydroxy-4-cholesten-3-one (C4) levels compared to Xbp1(fl/fl) mice, indicating reduced CYP7A1 synthetic activity...
December 30, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/28011707/fatty-acid-binding-profile-of-the-liver-x-receptor-alpha
#9
Shimpi Bedi, Genesis Victoria Hines, Valery V Lozada-Fernandez, Camila de Jesus Piva, Alagammai Kaliappan, S Dean Rider, Heather A Hostetler
Liver X receptor (LXR) alpha is a nuclear receptor that responds to oxysterols and cholesterol overload by stimulating cholesterol efflux, transport, conversion to bile acids, and excretion. LXR alpha binds to and is regulated by synthetic (T-0901317, GW3695) and endogenous (oxysterols) ligands. LXR alpha activity is also modulated by fatty acids (FA) but the ligand binding specificity of FA and acyl-CoA derivatives for LXR alpha remains unknown. We investigated whether LXR alpha binds FA or FA acyl-CoA with affinities that mimic in vivo concentrations, examined the effect of FA chain length and the degree of unsaturation on binding, and investigated if FA regulate LXR alpha activation...
December 23, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/28007964/peroxisome-proliferator-activated-receptor-%C3%AE-accelerates-%C3%AE-chlorofatty-acid-catabolism
#10
Elisa N D Palladino, Wen-Yi Wang, Carolyn J Albert, Cedric Langhi, Ángel Baldán, David A Ford
α-Chlorofatty aldehydes are generated from myeloperoxidase (MPO)-derived HOCl targeting plasmalogens, and are subsequently oxidized to α-chlorofatty acids (α-ClFA). The catabolic pathway for α-ClFA is initiated by ω-oxidation. Here we examine peroxisome proliferator-activated receptor-α; (PPAR-α) activation as a mechanism to increase α-ClFA catabolism. Pretreating both HepG2 cells and primary mouse hepatocytes with the PPAR-α agonist Wy 14643 increased the production of α-chlorodicarboxylic acids (α-ClDCA) in cells treated with exogenous α-ClFA...
December 22, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/28007846/different-origins-of-lysophospholipid-mediators-between-coronary-and-peripheral-arteries-in-acute-coronary-syndrome
#11
Makoto Kurano, Kuniyuki Kano, Tomotaka Dohi, Hirotaka Matsumoto, Koji Igarashi, Masako Nishikawa, Ryunosuke Ohkawa, Hitoshi Ikeda, Katsumi Miyauchi, Hiroyuki Daida, Junken Aoki, Yutaka Yatomi
Lysophosphatidic acids (LysoPA) and lysophosphatidylserine (LysoPS) are emerging lipid mediators proposed to be involved in the pathogenesis of acute coronary syndrome (ACS). In this study, we attempted to elucidate how LysoPA and LysoPS become elevated in ACS using human blood samples collected simultaneously from culprit coronary arteries and peripheral arteries in ACS subjects. We found that (1) the plasma LysoPA, LysoPS, and lysophosphatidylglycerol levels were not different, while the lysophosphatidylcholine (LysoPC), lysophosphatidylinositol, and lysophosphatidylethanolamine (LysoPE) levels were significantly lower in the culprit coronary arteries; (2) the serum ATX level was lower and the serum PS-PLA1 level was higher in the culprit coronary arteries; (3) the LysoPE and ATX levels were significant explanatory factors for the mainly elevated species of LysoPA, except for 22:6 LysoPA, in the peripheral arteries, while the LysoPC and LysoPE levels, but not the ATX level, were explanatory factors in the culprit coronary arteries; and (4) 18:0 and 18:1 LysoPS were significantly correlated with PS-PLA1 only in the culprit coronary arteries...
December 22, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27999147/quantitative-profiling-of-endocannabinoids-and-related-n-acylethanolamines-in-human-csf-using-nano-lc-ms-ms
#12
Vasudev Kantae, Shinji Ogino, Marek Noga, Amy C Harms, Robin M van Dongen, Gerrit L J Onderwater, Arn M J M van den Maagdenberg, Gisela M Terwindt, Mario van der Stelt, Michel D Ferrari, Thomas Hankemeier
Endocannabinoids, a class of lipid messengers, have emerged as crucial regulators of synaptic communication in the central nervous system (CNS). Dysregulation of these compounds has been implicated in many brain disorders. Although some studies have identified and quantified a limited number of target compounds, a method that provides comprehensive quantitative information on endocannabinoids and related N-acylethanolamines (NAEs) in CSF is currently lacking as measurements are challenging due to low concentrations under normal physiological conditions...
December 20, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27993949/unsupervised-analysis-of-combined-lipid-and-coagulation-data-reveal-coagulopathy-subtypes-among-dialysis-patients
#13
Daniel Contaifer, Daniel E Carl, Urszula Osinska Warncke, Erika J Martin, Bassem M Mohammed, Benjamin Van Tassell, Donald F Brophy, Charles Chalfant, Dayanjan S Wijesinghe
Hemodialysis and peritoneal dialysis are the primary means of managing end stage renal disease (ESRD). However, these treatment modalities are associated with the onset of coagulation abnormalities. Effective management of coagulation risk among these patients requires the identification of surrogate markers that provide an early indication of the coagulation abnormalities. The role of sphingolipids in the manifestation and prediction of coagulation abnormalities among dialysis patients have never been investigated...
December 19, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27993948/preferential-hydrolysis-of-truncated-oxidized-glycerophospholipids-by-lysosomal-phospholipase-a2
#14
Akira Abe, Miki Hiraoka, Hiroshi Ohguro, John J Tesmer, James A Shayman
Truncated oxidized-glycerophospholipids (ox-PLs) are bioactive lipids resulting from oxidative stress. The catabolic pathways for truncated ox-PLs are not fully understood. Lysosomal phospholipase A2 (LPLA2) with phospholipase A and transacylase activities is a key enzyme in phospholipid homeostasis. The present study assessed whether LPLA2 could hydrolyze truncated ox-PLs. Incubation of LPLA2 with liposomes consisting of 1,2-O-octadecenyl-sn-glycero-3-phosphocholine (DODPC)/1,2-dioleoyl-sn-glycero-3- phosphocholine (DOPC) or truncated oxidized phosphatidylcholine (ox-PC)/N-acetyl- sphingosine (NAS) under acidic conditions resulted in the preferential deacylation at the sn-1 position of the truncated ox-PCs...
December 19, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27974366/an-optimized-method-for-measuring-fatty-acids-and-cholesterol-in-stable-isotope-labeled-cells
#15
Joseph P Argus, Amy K Yu, Eric S Wang, Kevin J Williams, Steven J Bensinger
Stable isotope labeling has become an important methodology for determining lipid metabolic parameters of normal and neoplastic cells. Conventional methods for fatty acid and cholesterol analysis have one or more issues that limit their utility for in vitro stable isotope labeling studies. To address this, we developed a method optimized for measuring both fatty acids and cholesterol from small numbers of stable isotope labeled cultured cells. We demonstrate quantitative derivatization and extraction of fatty acids from a wide range of lipid classes using this approach...
December 14, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27956475/induction-of-fxr-signaling-in-germ-free-mice-colonized-with-a-human-microbiota
#16
Annika Wahlström, Petia Kovatcheva-Datchary, Marcus Ståhlman, Muhammad-Tanweer Khan, Fredrik Bäckhed, Hanns-Ulrich Marschall
: The gut microbiota influences the development and progression of metabolic diseases partly by metabolism of bile acids (BAs) and modified signaling through the farnesoid X receptor (FXR). In this study we aimed to determine how the human gut microbiota metabolizes murine BAs and affects FXR signaling in colonized mice. We colonized germ-free (GF) mice with caecal content from a mouse donor or faeces from a human donor and killed the mice after short term (2 weeks) or long term (15 weeks) colonization...
December 12, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27956474/on-the-importance-of-albumin-binding-for-the-flux-of-7%C3%AE-hydroxy-3-oxo-4-cholestenoic-acid-in-the-brain
#17
Ahmed A Saeed, Erik Edström, Irina Pikuleva, Gösta Eggertsen, Ingemar Björkhem
We confirmed previous findings by a Japanese group that there is an accumulation of 7α-hydroxy-3-oxo-4-cholestenoic acid (7-Hoca) in human subdural hematomas. The accumulation correlated with the time from the bleeding to the sample collection. We present evidence that these accumulations are likely to be caused by the strong affinity of 7-Hoca to albumin and the marked difference between plasma and brain with respect to levels of albumin. In the circulation 80-90 % of 7-Hoca is bound to albumin with a ratio between the steroid acid and albumin of about 1...
December 12, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27941027/the-lipid-droplet-associated-protein-perilipin-3-facilitates-hepatitis-c-virus-driven-hepatic-steatosis
#18
Daniel Ferguson, Jun Zhang, Matthew A Davis, Robert N Helsley, Lise-Lotte Vedin, Richard G Lee, Rosanne M Crooke, Mark J Graham, Paolo Parini, J Mark Brown
Hepatitis C Virus (HCV) is an enveloped RNA virus responsible for 170 million cases of viral hepatitis worldwide. Over 50% of chronically infected HCV patients develop hepatic steatosis, and steatosis can be induced by expression of HCV core protein (core) alone. Additionally, core must associate with cytoplasmic lipid droplets (LD) for steatosis development and viral particle assembly. Given the LD is an important component of hepatic lipid storage, and serves as a platform for HCV particle assembly; this dynamic subcellular organelle is a gatekeeper in the pathogenesis of viral hepatitis...
December 10, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27940482/quantitative-structural-characterization-of-phosphatidylinositol-phosphates-from-biological-samples
#19
Su Hee Kim, Ha Eun Song, Su Jung Kim, Dong Cheol Woo, Suhwan Chang, Woo Gyun Choi, Mi Jeong Kim, Sung Hoon Back, Hyun Ju Yoo
The aspects of cellular metabolism controlled by phosphatidylinositol phosphates (PtdInsPs) have been broadly expanded, and these phospholipids have drawn tremendous attention as pleiotropic signaling molecules. PtdInsPs analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) has remained challenging due to the strong hydrophilicity of these lipids. Multiple reaction monitoring (MRM) or a neutral loss scan has been performed to quantitatively measure PtdInsPs after chemical derivatization on the phosphate groups of inositol moieties...
December 9, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27940481/regulation-of-lipid-metabolism-by-obeticholic-acid-in-hyperlipidemic-hamsters
#20
Bin Dong, Mark Young, Xueqing Liu, Amar Bahadur Singh, Jingwen Liu
The farnesoid X receptor (FXR) plays critical roles in plasma cholesterol metabolism, in particular HDL-C homeostasis. Obeticholic acid (OCA) is a FXR agonist being developed for treating various chronic liver diseases. Previous studies reported inconsistent effects of OCA on regulating plasma cholesterol levels in different animal models and in different patient populations. The mechanisms underlying its divergent effects yet have not been thoroughly investigated. The scavenger receptor class B type I (SR-BI) is a FXR modulated gene and the major receptor for HDL-C...
December 9, 2016: Journal of Lipid Research
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