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Lipid droplet membrane proteome remodeling parallels ethanol-induced hepatic steatosis and its resolution. J. Lipid Res. (IF 4.483) Pub Date : 2021-02-19 Carol A Casey; Terrence M Donohue; Jacy L Kubik; Vikas Kumar; Michael J Naldrett; Nicholas T Woods; Cole P Frisbie; Mark A McNiven; Paul G Thomes
Lipid droplets (LDs) are composed of neutral lipids enclosed in a phospholipid monolayer, which harbors membrane-associated proteins that regulate LD functions. Despite the crucial role of LDs in lipid metabolism, remodeling of LD protein composition in disease contexts, such as steatosis, remains poorly understood. We hypothesized that chronic ethanol (EtOH) consumption, subsequent abstinence from
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Accurate quantification of lipid species affected by isobaric overlap in Fourier-Transform mass spectrometry. J. Lipid Res. (IF 4.483) Pub Date : 2021-02-15 Marcus Höring; Christer S Ejsing; Sabrina Krautbauer; Verena M Ertl; Ralph Burkhardt; Gerhard Liebisch
Lipidomics data require consideration of ions with near-identical masses, which comprises amongst others the Type-II isotopic overlap. This overlap occurs in series of lipid species differing only by number of double bonds (DB) mainly due to the natural abundance of 13C-atoms. High-resolution mass spectrometry, such as Fourier-Transform mass spectrometry (FTMS), is capable of resolving Type-II overlap
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Human Variant of Scavenger Receptor BI (R174C) Exhibits Impaired Cholesterol Transport Functions. J. Lipid Res. (IF 4.483) Pub Date : 2021-02-09 Sarah C May; Jacqueline S Dron; Robert A Hegele; Daisy Sahoo
HDL and its primary receptor, scavenger receptor BI (SR-BI), work together to promote the clearance of excess plasma cholesterol, thereby protecting against atherosclerosis. Human variants of SR-BI have been identified in patients with high HDL-cholesterol levels, and at least one variant has been linked to cardiovascular disease. Therefore, while often regarded as beneficial, very high levels of HDL-cholesterol
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Very long-chain fatty acid-containing lipids: a decade of novel insights from the study of ELOVL4. J. Lipid Res. (IF 4.483) Pub Date : 2021-02-05 Gyening Kofi Yeboah; Ekaterina S Lobanova; Richard S Brush; Martin-Paul Agbaga
Lipids play essential roles in maintaining cell structure and function by modulating membrane fluidity and cell signaling. The fatty acid elongase-4 (ELOVL4) protein - expressed in retina, brain, Meibomian glands, skin, testes and sperm - is an essential enzyme that mediates tissue-specific biosynthesis of both VLC-PUFA and VLC-saturated fatty acids (VLC-SFA). These fatty acids play critical roles
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Generation and validation of a conditional knockout mouse model for Desmosterolosis. J. Lipid Res. (IF 4.483) Pub Date : 2021-01-29 Babunageswararao Kanuri; Vincent Fong; Sithara Raju Ponny; Ranjuna Weerasekera; Kirthi Pulakanti; Kriya S Patel; Roman Tyshynsky; Shailendra B Patel
The enzyme 3β-hydroxysterol-Δ24 reductase (DHCR24, EC 1.3.1.72) catalyzes the conversion of desmosterol to cholesterol, and is obligatory for post-squalene cholesterol synthesis. Genetic loss of this enzyme results in Desmosterolosis (MIM #602398), a rare disease that presents with multiple congenital anomalies, features of which overlap with subjects with the Smith-Lemli-Opitz syndrome (another post-squalene
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Suppressing post-collection lysophosphatidic acid (LPA) metabolism improves the precision of plasma LPA quantification. J. Lipid Res. (IF 4.483) Pub Date : 2021-01-29 Kuniyuki Kano; Hirotaka Matsumoto; Nozomu Kono; Makoto Kurano; Yutaka Yatomi; Junken Aoki
Lysophosphatidic acid (LPA) is a potent signaling lipid, and state-dependent alterations in LPA make it a promising diagnostic marker for various diseases. However, plasma LPA concentrations vary widely among reports, even under normal conditions. These variations can be attributed, at least in part, to the artificial metabolism of LPA after blood collection, thus complicating the use of plasma LPA
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The lipid substrate preference of CETP controls the biochemical properties of HDL in fat/cholesterol-fed hamsters. J. Lipid Res. (IF 4.483) Pub Date : 2021-01-27 Richard E Morton; Daniel Mihna; Yan Liu
Cholesteryl ester transfer protein (CETP) modulates lipoprotein metabolism by transferring cholesteryl ester (CE) and triglyceride (TG) between lipoproteins. However, differences in the way CETP functions exist across species. Unlike human CETP, hamster CETP prefers TG over CE as a substrate, raising questions regarding how substrate preference may impact lipoprotein metabolism. To understand how altering
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Membrane therapy using DHA suppresses epidermal growth factor receptor signaling by disrupting nanocluster formation. J. Lipid Res. (IF 4.483) Pub Date : 2021-01-27 Natividad R Fuentes; Mohamed Mlih; Xiaoli Wang; Gabriella Webster; Sergio Cortes-Acosta; Michael L Salinas; Ian R Corbin; Jason Karpac; Robert S Chapkin
Epidermal growth factor receptor (EGFR) signaling drives the formation of many types of cancer, including colon cancer. Docosahexaenoic acid (DHA, 22∶6Δ4,7,10,13,16,19), a chemoprotective long chain n-3 polyunsaturated fatty acid (PUFA) suppresses EGFR signaling. However, the mechanism underlying this phenotype remains unclear. Therefore, we used super-resolution microscopy techniques to investigate
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An advanced method for propargylcholine phospholipid detection by direct-infusion mass spectrometry. J. Lipid Res. (IF 4.483) Pub Date : 2021-01-13 Mohamed H Yaghmour; Christoph Thiele; Lars Kuerschner
Phospholipids with a choline head group are an abundant component of cellular membranes and are involved in many important biological functions. For studies on the cell biology and metabolism of these lipids traceable analogues where propargylcholine replaces the choline head group have proven useful. We present a novel method to analyze propargylcholine phospholipids by mass spectrometry. The routine
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Mass spectrometry imaging of phosphatidylcholine metabolism in lungs administered with therapeutic surfactants and isotopic tracers. J. Lipid Res. (IF 4.483) Pub Date : 2021-01-13 Shane R Ellis; Emily Hall; Madhuriben Panchal; Bryn Flinders; Jens Madsen; Grielof Koster; Ron M A Heeren; Howard W Clark; Anthony D Postle
Mass spectrometry imaging (MSI) visualises molecular distributions throughout tissues but is blind to dynamic metabolic processes. Here, MSI with high mass resolution together with multiple stable isotope labelling provided spatial analyses of phosphatidylcholine (PC) metabolism in mouse lungs. Dysregulated surfactant metabolism is central to many respiratory diseases. Metabolism and turnover of therapeutic
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Perioperative high-density lipoproteins, oxidative stress, and kidney injury after cardiac surgery. J. Lipid Res. (IF 4.483) Pub Date : 2021-01-13 Loren E Smith; Derek K Smith; Patricia G Yancey; Valentina Kon; Alan T Remaley; Frederic T Billings; MacRae F Linton
Oxidative stress promotes acute kidney injury (AKI). Higher concentrations of HDL cholesterol are associated with less AKI. To test the hypothesis that HDL antioxidant activity is associated with AKI after cardiac surgery, we quantified HDL particle size and number, paraoxonase-1 activity, and isofuran concentrations in 75 patients who developed AKI and 75 matched control patients. Higher preoperative
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Palmitoylation of acetylated tubulin and association with ceramide-rich platforms is critical for ciliogenesis. J. Lipid Res. (IF 4.483) Pub Date : 2020-12-30 Priyanka Tripathi; Zhihui Zhu; Haiyan Qin; Ahmed Elsherbini; Simone M Crivelli; Emily Roush; Guanghu Wang; Stefka D Spassieva; Erhard Bieberich
Microtubules are polymers composed of αβ-tubulin subunits that provide structure to cells and play a crucial role in in the development and function of neuronal processes and cilia, microtubule-driven extensions of the plasma membrane that have sensory (primary cilia) or motor (motile cilia) functions. To stabilize microtubules in neuronal processes and cilia, α tubulin is modified by the posttranslational
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Human glucocerebrosidase mediates formation of xylosyl-cholesterol by β-xylosidase and transxylosidase reactions. J. Lipid Res. (IF 4.483) Pub Date : 2020-12-23 Daphne E C Boer; Mina Mirzaian; Maria J Ferraz; Kimberley C Zwiers; Merel V Baks; Marc D Hazeu; Roelof Ottenhoff; Andre R A Marques; Rianne Meijer; Jonathan P C Roos; Timothy M Cox; Rolf G Boot; Navraj Pannu; Herman S Overkleeft; Marta Artola; Johannes M F G Aerts
Deficiency of glucocerebrosidase (GBA), a lysosomal β-glucosidase, causes Gaucher disease. The enzyme hydrolyzes β-glucosidic substrates and transglucosylates cholesterol to cholesterol-β-glucoside. Here we show that recombinant human GBA also cleaves β-xylosides and transxylosylates cholesterol. The xylosyl-cholesterol formed acts as acceptor for subsequent formation of di-xylosyl-cholesterol. Common
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Lipid metabolism dysregulation in diabetic retinopathy. J. Lipid Res. (IF 4.483) Pub Date : 2020-12-23 Julia V Busik
Lipid metabolic abnormalities have emerged as potential risk factors for the development and progression of diabetic complications, including diabetic retinopathy (DR). This review article provides an overview of the results of clinical trials evaluating the potential benefits of lipid lowering drugs, such as fibrates, omega 3 fatty acids, and statins, for the prevention and treatment of DR. Although
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Lipid signature of advanced human carotid atherosclerosis assessed by mass spectrometry imaging. J. Lipid Res. (IF 4.483) Pub Date : 2020-12-23 Astrid M Moerman; Mirjam Visscher; Nuria Slijkhuis; Kim Van Gaalen; Bram Heijs; Theo Klein; Peter C Burgers; Yolanda B De Rijke; Heleen M M Van Beusekom; Theo M Luider; Hence J M Verhagen; Antonius F W Van der Steen; Frank J H Gijsen; Kim Van der Heiden; Gijs Van Soest
Carotid atherosclerosis is a risk factor for ischemic stroke, one of the main causes of mortality and disability worldwide. The disease is characterized by plaques, heterogeneous deposits of lipids and necrotic debris in the vascular wall, which grow gradually and may remain asymptomatic for decades. However, at some point a plaque can evolve to a high-risk plaque phenotype, which may trigger a cerebrovascular
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Gene Networks and Pathways for Plasma Lipid Traits via Multi-tissue Multi-omics Systems Analysis. J. Lipid Res. (IF 4.483) Pub Date : 2020-12-23 Montgomery Blencowe; In Sook Ahn; Zara Saleem; Helen Luk; Ingrid Cely; Ville-Petteri Mäkinen; Yuqi Zhao; Xia Yang
Genome-wide association studies (GWAS) have implicated ~380 genetic loci for plasma lipid regulation. However, these loci only explain 17-27% of the trait variance and a comprehensive understanding of the molecular mechanisms has not been achieved. In this study, we utilized an integrative genomics approach leveraging diverse genomic data from human populations to investigate whether genetic variants
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Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control. J. Lipid Res. (IF 4.483) Pub Date : 2020-12-17 Stacey N Keenan; William DeNardo; Jieqiong Lou; Ralf B Schittenhelm; Magdalene K Montgomery; James G Granneman; Elizabeth Hinde; Matthew J Watt
Perilipin (PLIN) 5 is a lipid droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). We sought to identify PKA phosphorylation sites in PLIN5 and assess their functional relevance in cultured cells and the livers of mice. We detected phosphorylation on S155
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Deletion of lysophosphatidylcholine acyltransferase3 in myeloid cells worsens hepatic steatosis after a high fat diet. J. Lipid Res. (IF 4.483) Pub Date : 2020-12-11 Thibaut Bourgeois; Antoine Jalil; Charles Thomas; Charlene Magnani; Naig Le Guern; Thomas Gautier; Jean-Paul Pais DE Barros; Victoria Bergas; Hélène Choubley; Loic Mazzeo; Louise Menegaut; Lorene Lebrun; Kevin Van Dongen; Marion Xolin; Tony Jourdan; Chloe Buch; Jérôme Labbé; Philippe Saas; Laurent Lagrost; David Masson; Jacques Grober
Recent studies have highlighted an important role for lysophosphatidylcholine acyltransferase 3 (LPCAT3) in controlling the PUFA composition of cell membranes in the liver and intestine. In these organs, LPCAT3 critically supports cell membrane-associated processes such as lipid absorption or lipoprotein secretion. However, the role of LPCAT3 in macrophages remains controversial. Here, we investigated
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Distinct patterns of apolipoprotein C-I, C-II and C-III isoforms are associated with markers of Alzheimer's disease. J. Lipid Res. (IF 4.483) Pub Date : 2020-12-11 Yueming Hu; Cristiana Meuret; Ashley Martinez; Hussein Yassine; Dobrin Nedelkov
Apolipoproteins C-I, C-II and C-III interact with ApoE to regulate lipoprotein metabolism and contribute to Alzheimer's disease pathophysiology. In plasma, apoC-I and C-II exist as truncated isoforms, while apoC-III exhibits multiple glycoforms. This study aimed to 1. delineate apoC-I, C-II and C-III isoform profiles in CSF and plasma in a cohort of non-demented older individuals (n = 61), and 2. examine
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Mutation in the distal NPxY motif of LRP1 alleviates dietary cholesterol-induced dyslipidemia and tissue inflammation. J. Lipid Res. (IF 4.483) Pub Date : 2020-12-09 Anja Jaeschke; April Haller; James G Cash; Christopher Nam; Emily Igel; Anton J M Roebroek; David Y Hui
The LDL receptor-related protein-1 (LRP1) is highly expressed in numerous cell types, and its impairment is associated with obesity, diabetes, and fatty liver disease. However, the mechanisms linking LRP1 to metabolic disease are not completely understood. Here, we compared the metabolic phenotype of C57BL/6J wild type and LRP1 knock-in mice carrying an inactivating mutation in the distal NPxY motif
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Human CETP lacks lipopolysaccharide transfer activity, but worsens inflammation and sepsis outcomes in mice. J. Lipid Res. (IF 4.483) Pub Date : 2020-12-09 Aloïs Dusuel; Valérie Deckert; Jean-Paul Pais DE Barros; Kevin Van Dongen; Hélène Choubley; Emilie Charron; Naig Le Guern; Jérôme Labbé; Stéphane Mandard; Jacques Grober; Laurent Lagrost; Thomas Gautier
Bacterial lipopolysaccharides (LPSs or endotoxins) can bind most proteins of the lipid transfer/LPS-binding protein (LT/LBP) family in host organisms. The LPS-bound LT/LBP proteins then trigger either an LPS-induced proinflammatory cascade or LPS binding to lipoproteins that are involved in endotoxin inactivation and detoxification. Cholesteryl ester transfer protein (CETP) is an LT/LBP member, but
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rHDL modelling and the anchoring mechanism of LCAT activation. J. Lipid Res. (IF 4.483) Pub Date : 2020-12-02 Tommaso Laurenzi; Chiara Parravicini; Luca Palazzolo; Uliano Guerrini; Elisabetta Gianazza; Laura Calabresi; Ivano Eberini
Lecithin:cholesterol-acyl-transferase (LCAT) plays a major role in cholesterol metabolism as it is the only extracellular enzyme able to esterify cholesterol. LCAT activity is required for lipoprotein remodelling and, most specifically, for the growth and maturation of HDLs. In fact, genetic alterations affecting LCAT func- tionality may cause a severe reduction in plasma levels of HDL-cholesterol
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Structure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux. J. Lipid Res. (IF 4.483) Pub Date : 2020-11-17 Oktawia Nilsson; Mikaela Lindvall; Laura Obici; Simon Ekström; Jens O Lagerstedt; Rita Del Giudice
Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) is essential for the transportation of cholesterol between peripheral tissues and the liver. However, specific mutations in Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) are responsible for a late-onset systemic amyloidosis, the pathological accumulation of protein fibrils in tissues and organs. Carriers of these mutations
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Insights on the kinetics and dynamics of the furin-cleaved form of PCSK9. J. Lipid Res. (IF 4.483) Pub Date : 2020-11-17 Carlota Oleaga; Joshua Hay; Emma Gurcan; Larry L David; Paul A Mueller; Hagai Tavori; Michael D Shapiro; Nathalie Pamir; Sergio Fazio
Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates cholesterol metabolism by inducing the degradation of hepatic low-density lipoprotein receptor (LDLR). Plasma PCSK9 has two main molecular forms: a 62-kDa mature form (PCSK9_62) and a 55-kDa, furin-cleaved form (PCSK9_55). PCSK9_55 is considered less active than PCSK9_62 in degrading LDLR. We aimed to identify the site of PCSK9_55 formation
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Generation and validation of a conditional knockout mouse model for the study of the Smith-Lemli-Opitz Syndrome. J. Lipid Res. (IF 4.483) Pub Date : 2020-11-17 Babunageswararao Kanuri; Vincent Fong; Sithara Raju Ponny; Keri A Tallman; Sriganesh Ramachandra Rao; Ned A Porter; Steven J Fliesler; Shailendra B Patel
Smith-Lemli-Opitz Syndrome (SLOS) is a developmental disorder (OMIM #270400) caused by autosomal recessive mutations in the Dhcr7 gene, which encodes the enzyme 3β-hydroxysterol-∆7 reductase. SLOS patients present clinically with dysmorphology and neurological, behavioral and cognitive defects, with characteristically elevated levels of 7-dehydrocholesterol (7-DHC) in all bodily tissues and fluids
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Adiponectin forms a complex with atherogenic LDL and inhibits its downstream effects. J. Lipid Res. (IF 4.483) Pub Date : 2020-11-03 Akemi Kakino; Yoshiko Fujita; Liang-Yin Ke; Hua-Chen Chan; Ming-Hsien Tsai; Chia-Yen Dai; Chu-Huang Chen; Tatsuya Sawamura
Adiponectin, an adipocyte-derived protein, has anti-atherogenic and anti-diabetic effects, but how it confers the anti-atherogenic effects is not well understood. To study the anti-atherogenic mechanisms of adiponectin, we examined whether it interacts with atherogenic low-density lipoprotein (LDL) to attenuate LDL's atherogenicity. L5, the most electronegative subfraction of LDL, induces atherogenic
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Bioavailability and spatial distribution of fatty acids in the rat retina after dietary omega-3 supplementation. J. Lipid Res. (IF 4.483) Pub Date : 2020-10-30 Elisa Vidal; Bokkyoo Jun; William C Gordon; Marie-Annick Maire; Lucy Martine; Stéphane Grégoire; Spiro Khoury; Stephanie Cabaret; Olivier Berdeaux; Niyazi Acar; Lionel Bretillon; Nicolas G Bazan
Spatial changes of fatty acids in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids, EPA-containing triglycerides, DHA-containing phospholipids, or
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Overview of how N32 and N34 elovanoids sustain sight by protecting retinal pigment epithelial cells and photoreceptors. J. Lipid Res. (IF 4.483) Pub Date : 2020-10-26 Nicolas G Bazan
The essential fatty acid DHA (22:6, omega-3 or n-3) is enriched in and required for the membrane biogenesis and function of photoreceptor cells (PRC), synapses, mitochondria, etc. of the CNS. PRC DHA becomes an acyl chain at the sn-2 of phosphatidylcholine (PC), amounting to more than 50% of the PRC outer segment phospholipids, where phototransduction takes place. Very long chain PUFAs (VLC-PUFAs,n-3
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Depletion of essential isoprenoids and ER stress induction following acute liver-specific deletion of HMG-CoA Reductase. J. Lipid Res. (IF 4.483) Pub Date : 2020-10-27 Marco De Giorgi; Kelsey E Jarrett; Jason C Burton; Alexandria M Doerfler; Ayrea Hurley; Ang Li; Rachel H Hsu; Mia Furgurson; Kalyani R Patel; Jun Han; Christoph H Borchers; William R Lagor
HMG-CoA Reductase (Hmgcr) is the rate-limiting enzyme in the mevalonate pathway and is inhibited by statins. In addition to cholesterol, Hmgcr activity is also required for synthesizing non-sterol isoprenoids, such as dolichol, ubiquinone, farnesylated and geranylgeranylated proteins. Here, we investigated the effects of Hmgcr inhibition on non-sterol isoprenoids in the liver. We have generated new
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High-density lipoprotein-associated miRNA is increased following Roux-en-Y gastric bypass surgery for severe obesity. J. Lipid Res. (IF 4.483) Pub Date : 2020-10-22 Jan Hoong Ho; Kwok Leung Ong; Luisa F Cuesta Torres; Yifen Liu; Safwaan Adam; Zohaib Iqbal; Shaishav Dhage; Basil J Ammori; Akheel A Syed; Kerry-Anne Rye; Fatiha Tabet; Handrean Soran
Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed weight-loss procedures, but how severe obesity and RYGB affects circulating HDL-associated microRNAs (miRNAs) remains unclear. Here, we aim to investigate how HDL-associated miRNAs are regulated in severe obesity and how weight loss after RYGB surgery affects HDL-miRNAs. Plasma HDL were isolated from patients with severe obesity
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Cholesterol homeostasis in the vertebrate retina: Biology and pathobiology. J. Lipid Res. (IF 4.483) Pub Date : 2020-10-20 Sriganesh Ramachandra Rao; Steven J Fliesler
Cholesterol is a quantitatively and biologically significant constituent of all mammalian cell membrane, including those that comprise the retina. Retinal cholesterol homeostasis entails the interplay between de novo synthesis, uptake, intra-retinal sterol transport, metabolism and efflux. Defects in these complex processes are associated with several congenital and age-related disorders of the visual
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LDL-apheresis as an alternate method for plasma LPS purification in healthy volunteers, dyslipidemic and septic patients. J. Lipid Res. (IF 4.483) Pub Date : 2020-10-09 Auguste Dargent; Jean-Paul Pais DE Barros; Samir Saheb; Randa Bittar; Wilfried Le Goff; Alain Carrié; Thomas Gautier; Isabelle Fournel; Anne-Laure Rérole; Hélène Choubley; David Masson; Laurent Lagrost; Jean-Pierre Quenot
Lipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for sepsis treatment, as antibiotics are not sufficient to improve outcome during septic shock. Extracorporeal removal method by polymyxin B hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP therapy. PMX-DHP has
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Update on LIPID MAPS Classification, Nomenclature and Shorthand Notation for MS-derived Lipid Structures. J. Lipid Res. (IF 4.483) Pub Date : 2020-10-09 Gerhard Liebisch; Eoin Fahy; Junken Aoki; Edward A Dennis; Thierry Durand; Christer Ejsing; Maria Fedorova; Ivo Feussner; William J Griffiths; Harald Koefeler; Alfred H Merrill; Robert C Murphy; Valerie B O'Donnell; Olga V Oskolkova; Shankar Subramaniam; Michael Wakelam; Friedrich Spener
A comprehensive and standardized system to report lipid structures analyzed by mass spectrometry is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols
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Insulin resistance dysregulates CYP7B1 leading to oxysterol accumulation: a pathway for NAFL to NASH transition. J. Lipid Res. (IF 4.483) Pub Date : 2020-10-02 Genta Kakiyama; Dalila Marques; Rebecca Martin; Hajime Takei; Daniel Rodriguez-Agudo; Sandra A LaSalle; Taishi Hashiguchi; Xiaoying Liu; Richard M Green; Sandra K Erickson; Gregorio Gil; Michael Fuchs; Mitsuyoshi Suzuki; Tsuyoshi Murai; Hiroshi Nittono; Phillip B Hylemon; Huiping Zhou; William M Pandak
Nonalcoholic fatty liver disease (NAFLD) is an important public health issue closely associated with the pervasive epidemics of diabetes and obesity. Yet, despite NAFLD being among the most common of chronic liver diseases, the biological factors responsible for its transition from benign nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) remain unclear. This lack of knowledge leads
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Hsa-miR-23a-3p promotes atherogenesis in a novel mouse model of atherosclerosis. J. Lipid Res. (IF 4.483) Pub Date : 2020-10-02 Jiayan Guo; Hanbing Mei; Zhen Sheng; Qingyuan Meng; Murielle M Veniant; Hong Yin
Of the known regulators of atherosclerosis, miRNAs have been demonstrated to play critical roles in lipoprotein homeostasis and plaque formation. Here, we generated a novel animal model of atherosclerosis by knocking-in LDLRW483X in C57BL/6 mice, as the W483X mutation in LDLR is considered the most common, newly identified pathogenic mutation in Chinese familial hypercholesterolemia (FH) individuals
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Progression of chronic kidney disease in Familial LCAT Deficiency: a follow-up of the Italian cohort. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-30 Chiara Pavanello; Alice Ossoli; Marcello Arca; Laura D'Erasmo; Giuliano Boscutti; Loreto Gesualdo; Tiziano Lucchi; Tiziana Sampietro; Fabrizio Veglia; Laura Calabresi
Familial LCAT deficiency (FLD) is a rare genetic disorder of HDL metabolism, caused by loss-of-function mutations in the LCAT gene and characterized by a variety of symptoms including corneal opacities and kidney failure. Renal disease represents the leading cause of morbidity and mortality in FLD cases. However, the prognosis is not known and the rate of deterioration of kidney function is variable
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Identification of Unusual Phospholipids from Bovine Heart Mitochondria by HPLC-MS/MS. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-30 Junhwan Kim; Charles L Hoppel
Phospholipids, including ether phospholipids, are composed of numerous isomeric and isobaric species that have the same backbone and acyl chains. This structural resemblance results in similar fragmentation patterns by collision-induced dissociation of phospholipids regardless of class, yielding complicated tandem mass spectrometry (MS/MS) spectra when isobaric species are analyzed together. Furthermore
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Nuclear translocation ability of Lipin differentially affects gene expression and survival in fed and fasting Drosophila. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-28 Stephanie E Hood; Xeniya V Kofler; Quiyu Chen; Judah Scott; Jason Ortega; Michael Lehmann
Lipins are eukaryotic proteins with functions in lipid synthesis and the homeostatic control of energy balance. They execute these functions by acting as phosphatidate phosphatase enzymes in the cytoplasm and by changing gene expression after translocation into the cell nucleus, in particular under fasting conditions. Here, we asked whether nuclear translocation and enzymatic activity of Drosophila
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Myeloid deletion and therapeutic activation of AMPK do not alter atherosclerosis in male or female mice. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-25 Nicholas D LeBlond,Peyman Ghorbani,Conor O'Dwyer,Nia Ambursley,Julia Rc Nunes,Tyler Kt Smith,Natasha A Trzaskalski,Erin E Mulvihill,Benoit Viollet,Marc Foretz,Morgan D Fullerton
The dysregulation of myeloid-derived cell metabolism can drive atherosclerosis. AMP-activated protein kinase (AMPK) controls various aspects of macrophage dynamics and lipid homeostasis, which are important during atherogenesis. Using LysM-Cre to drive the deletion of both the α1 and α2 catalytic subunits (MacKO), we aimed to clarify the role of myeloid-specific AMPK signaling in male and female mice
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SCD1 Promotes Lipid Mobilization in Subcutaneous White Adipose Tissue. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-25 Ying Zou,Yi-Na Wang,Hong Ma,Zhi-Hui He,Yan Tang,Liang Guo,Yang Liu,Meng Ding,Shuwen Qian,Qi-Qun Tang
Beiging of white adipose tissue has beneficial effects on metabolism. Although it is known that beige adipocytes are active in lipid catabolism and thermogenesis, how it is regulated deserve more explorations. In this study, we demonstrate that stearoyl-CoA desaturase 1 (SCD1) in subcutaneous white adipose tissue (scWAT) responded to cold stimulation and was able to promote mobilization of triglyceride
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Characterization of Essential Domains in HSD17B13 for Cellular Localization and Enzymatic Activity. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-24 Yanling Ma; Suman Karki; Philip M Brown; Dennis D Lin; Maren C Podszun; Wenchang Zhou; Olga V Belyaeva; Natalia Y Kedishvili; Yaron Rotman
Recently, human genetic studies identified an association of single-nucleotide polymorphisms (SNPs) in the HSD17B13 (17-beta hydroxysteroid dehydrogenase 13) gene with alcoholic and nonalcoholic fatty liver disease (NAFLD) development. Mutant HSD17B13 variants devoid of enzymatic function have been demonstrated to be protective from cirrhosis and liver cancer, supporting the development of HSD17B13
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A review of phosphatidate phosphatase assays. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-22 Prabuddha Dey,Gil-Soo Han,George M Carman
Phosphatidate phosphatase catalyzes the penultimate step in the synthesis of triacylglycerol and regulates the synthesis of membrane phospholipids. There is much interest in this enzyme because it controls the cellular levels of its substrate phosphatidate and product diacylglycerol; defects in the metabolism of these lipid intermediates are the basis for lipid-based diseases such as obesity, lipodystrophy
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β-carotene conversion to vitamin A delays atherosclerosis progression by decreasing hepatic lipid secretion in mice. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-22 Felix Zhou,Xiaoyun Wu,Ivan Pinos,Benjamin M Abraham,Tessa J Barrett,Johannes von Lintig,Edward A Fisher,Jaume Amengual
Atherosclerosis is characterized by the pathological accumulation of cholesterol-laden macrophages in the arterial wall. Atherosclerosis is also the main underlying cause of cardiovascular diseases (CVDs), and its development is largely driven by elevated plasma cholesterol. Strong epidemiological data find an inverse association between plasma β-carotene with atherosclerosis, and we recently showed
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PLRP2 selectively localizes synaptic membrane proteins via acyl-chain remodeling of phospholipids. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-22 Hideaki Kuge,Izumi Miyamoto,Ken-Ichi Yagyu,Koichi Honke
The plasma membrane of neurons consists of distinct domains, each of which carries specialized functions and a characteristic set of membrane proteins. While this compartmentalized membrane organization is essential for neuronal functions, it remains controversial how neurons establish these domains on the laterally fluid membrane. Here, using immunostaining, lipid-MS analysis and gene ablation with
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Chylomicronemia from GPIHBP1 autoantibodies. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-18 Kazuya Miyashita,Jens Lutz,Lisa C Hudgins,Dana Toib,Ambika P Ashraf,Wenxin Song,Masami Murakami,Katsuyuki Nakajima,Michael Ploug,Loren G Fong,Stephen G Young,Anne P Beigneux
Some cases of chylomicronemia are caused by autoantibodies against GPIHBP1, an endothelial cell protein that shuttles lipoprotein lipase (LPL) to the capillary lumen. GPIHBP1 autoantibodies prevent binding and transport of LPL by GPIHBP1, thereby disrupting the lipolytic processing of triglyceride-rich lipoproteins. Here, we review the "GPIHBP1 autoantibody syndrome" and summarize clinical and laboratory
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Sphingolipids as Critical Players in Retinal Physiology and Pathology. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-18 Maria Victoria Simon,Sandip K Basu,Bano Qaladize,Richard C Grambergs,Nora P Rotstein,Nawajes Mandal
Sphingolipids have emerged as bioactive lipids involved in the regulation of many physiological and pathological processes. In the retina, they have been established to participate in numerous processes, such as neuronal survival and death, proliferation and migration of neuronal and vascular cells, inflammation, and neovascularization. Dysregulation of sphingolipids is, therefore, crucial in the onset
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Sterol Regulatory Element-Binding Protein Sre1 regulates carotenogenesis in the red yeast Xanthophyllomyces dendrorhous. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-15 Melissa Gómez,Sebastián Campusano,María Soledad Gutiérrez,Dionisia Sepúlveda,Salvador Barahona,Marcelo Baeza,Victor Cifuentes,Jennifer Alcaíno
Xanthophyllomyces dendrorhous is a basidiomycete yeast that produces carotenoids, mainly astaxanthin. Astaxanthin is an organic pigment of commercial interest due to its antioxidant and coloring properties. X. dendrorhous has a functional Sterol Regulatory Element-Binding Protein (SREBP) pathway, and the Sre1 protein is the SREBP homolog in this yeast. However, how Sre1 is promoting the biosynthesis
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Stimulation of the ATPase activity of MDR3/ABCB4 requires an intact phosphatidylcholine lipid. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-11 Martin Prescher,Sander H J Smits,Lutz Schmitt
ABCB4/MDR3 is located in the canalicular membrane of hepatocytes and translocates phosphatidylcholine (PC) lipids from the cytoplasmic to the extracellular leaflet. ABCB4 is an ATP-dependent transporter that reduces the harsh detergent effect of the bile salts by counteracting self-digestion. To do so ABCB4 provides PC-lipids for extraction into bile. PC-lipids account for 40% of the entire pool of
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A novel phosphoglycerol serine-glycine lipodipeptide of Porphyromonas gingivalis is a TLR2 ligand. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-10 Frank C Nichols,Robert B Clark,Mark W Maciejewski,Anthony A Provatas,Jeremy L Balsbaugh,Floyd E Dewhirst,Michael B Smith,Amanda Rahmlow
Porphyromonas gingivalis is a Gram-negative anaerobic periodontal microorganism strongly associated with tissue destructive processes in human periodontitis. Following oral infection with P. gingivalis, the periodontal bone loss in mice is reported to require engagement of Toll-like receptor 2 (TLR2). Serine-glycine lipodipeptide or glycine aminolipid classes of P. gingivalis engage human and mouse
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Membrane bound diacylglycerols explain the dissociation of hepatic insulin resistance from steatosis in MTTP-/- mice. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-09 Abudukadier Abulizi,Daniel F Vatner,Zhang Ye,Yongliang Wang,Joao-Paulo Camporez,Dongyan Zhang,Mario Kahn,Kun Lyu,Alaa Sirwi,Gary W Cline,M Mahmood Hussain,Patrícia Aspichueta,Varman T Samuel,Gerald I Shulman
Microsomal triglyceride transfer protein (MTTP) deficiency results in a syndrome of hypolipidemia and accelerated nonalcoholic fatty liver disease (NAFLD). Animal models of decreased hepatic MTTP activity have revealed an unexplained dissociation between hepatic steatosis and hepatic insulin resistance. Here, we performed comprehensive metabolic phenotyping of liver specific MTTP knockout (L-Mttp-/-)
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Cholesterol transport between red blood cells and lipoproteins contributes to cholesterol metabolism in blood. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-09 Ryunosuke Ohkawa,Hann Low,Nigora Mukhamedova,Ying Fu,Shao-Jui Lai,Mai Sasaoka,Ayuko Hara,Azusa Yamazaki,Takahiro Kameda,Yuna Horiuchi,Peter J Meikle,Gerard Pernes,Graeme I Lancaster,Michael Ditiatkovski,Paul Nestel,Boris L Vaisman,Denis Sviridov,Andrew J Murphy,Alan T Remaley,Dmitri Sviridov,Minoru Tozuka
Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities of free cholesterol in their membrane, play an important role in reverse cholesterol transport. However, the exact role of RBCs in systemic cholesterol metabolism is poorly understood. RBCs were incubated with autologous plasma
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High Resolution Structure of Human Apolipoprotein (a) Kringle IV Type 2: Beyond the Lysine Binding Site. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-09 Alice Santonastaso,Maristella Maggi,Hugo De Jonge,Claudia Scotti
Lipoprotein (a) [Lp(a)] is characterized by an LDL-like composition in terms of lipids and apoB100, and by one copy of a unique glycoprotein, apolipoprotein (a) [apo(a)]. The apo(a) structure is mainly based on the repetition of tandem kringle domains with high homology to plasminogen kringles 4 and 5. Among them, kringle IV type 2 (KIV-2) is present in a highly variable number of genetically encoded
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Lipid and Metabolic Syndrome Traits in Coronary Artery Disease: A Mendelian Randomization Study. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-09 David G Thomas,Ying Wei,Alan R Tall
Mendelian randomization (MR) of lipid traits in coronary artery disease (CAD) has provided evidence for causal associations of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) in CAD, but many lipid trait genetic variants have pleiotropic effects on other cardiovascular risk factors that may bias MR associations. The goal of this study was to evaluate pleiotropic effects of lipid
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Assessing the role of glycosphingolipids in the phenotype severity of Fabry disease mouse model. J. Lipid Res. (IF 4.483) Pub Date : 2020-08-31 Siamak Jabbarzadeh-Tabrizi,Michel Boutin,Taniqua S Day,Mouna Taroua,Raphael Schiffmann,Christiane Auray-Blais,Jin-Song Shen
Fabry disease is caused by deficient activity of α-galactosidase A-an enzyme that hydrolyses the terminal α-galactosyl moieties from glycolipids and glycoproteins--and subsequent accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3), globotriaosylsphingosine (lyso-Gb3) and galabiosylceramide. However, there is no known link between these compounds and disease severity. In this study
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Time for a détente in the war on the mechanism of cellular fatty acid uptake. J. Lipid Res. (IF 4.483) Pub Date : 2020-09-01 Jan F C Glatz,Joost J F P Luiken
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Hepatic Deletion of Mboat7 (Lpiat1) Causes Activation of SREBP-1c and Fatty Liver. J. Lipid Res. (IF 4.483) Pub Date : 2020-08-28 Mingfeng Xia,Preethi Chandrasekaran,Shunxing Rong,Xiaorong Fu,Matthew A Mitsche
Genetic variants that increase the risk of fatty liver disease (FLD) and cirrhosis have recently been identified in the proximity of membrane bound O-acyltransferase domain-containing 7 (MBOAT7). To elucidate the link between these variants and FLD we characterized Mboat7 liver-specific knock-out mice (Mboat7-LSKO). Chow-fed Mboat7-LSKO mice developed fatty livers and associated liver injury. Lipidomic
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The anti-tubercular activity of simvastatin is mediated by cholesterol-driven autophagy via the AMPK-mTORC1-TFEB axis. J. Lipid Res. (IF 4.483) Pub Date : 2020-08-26 Natalie Bruiners,Noton Dutta,Valentina Guerrini,Hugh Salamon,Ken D Yamaguchi,Petros C Karakousis,Maria Laura Gennaro
The rise of drug-resistant tuberculosis (TB) poses a major risk to public health. Statins, which inhibit both cholesterol biosynthesis and protein prenylation branches of the mevalonate pathway, increase anti-tubercular antibiotic efficacy in animal models. However, the underlying molecular mechanisms are unknown. In this study, we used an in vitro macrophage infection model to investigate simvastatin's
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Harmonized procedures lead to comparable quantification of total oxylipins across laboratories. J. Lipid Res. (IF 4.483) Pub Date : 2020-08-26 Malwina Mainka,Céline Dalle,Mélanie Pétéra,Jessica Dalloux-Chioccioli,Nadja Kampschulte,Annika I Ostermann,Michael Rothe,Justine Bertrand-Michel,John W Newman,Cécile Gladine,Nils Helge Schebb
Oxylipins are potent lipid mediators involved in a variety of physiological processes. Their profiling has the potential to provide a wealth of information regarding human health and disease and is a promising technology for translation into cli