10,891 results match your criteria Journal of Lipid Research[Journal]


Use of Isotopically Labelled Substrates Reveals Kinetic Differences Between Human and Bacterial Serine Palmitoyltransferase.

J Lipid Res 2019 Feb 21. Epub 2019 Feb 21.

University of Edinburgh, United Kingdom;

Isotope labels are frequently used tools to track metabolites through complex biochemical pathways and to discern the mechanisms of enzyme-catalysed reactions. Isotopically-labelled L-serine is often used to monitor the activity of the first enzyme in sphingolipid biosynthesis, serine palmitoyltransferase (SPT) as well as labelling downstream cellular metabolites. Intrigued by the effect that isotope labels may be having on SPT catalysis, we characterised the impact of different L-serine isotopologues on the catalytic activity of recombinant SPT isozymes from humans and the bacterium Sphingomonas paucimobilis. Read More

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http://dx.doi.org/10.1194/jlr.M089367DOI Listing
February 2019

Regulatory T cells suppress excessive lipid accumulation in alcoholic liver disease.

J Lipid Res 2019 Feb 21. Epub 2019 Feb 21.

Huazhong University of Science and Technology, China

Sensitization hepatic immune cells of chronic alcoholic consumption gives rise to inflammatory accumulation which is considered as leading cause to liver damage. T regulatory cells (Tregs) are immunosuppressive cell subset that play an important role in a variety of liver diseases, however, data about pathological involvement of Tregs in liver steatosis of ALD is insufficient. In mouse models of ALD, we found that increased lipid accumulation by chronic alcohol intake as companioned with oxidative stress, inflammatory accumulation as well as Treg decline in the liver. Read More

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http://dx.doi.org/10.1194/jlr.M083568DOI Listing
February 2019

Inflammasomes, Neutrophil Extracellular Traps, and Cholesterol.

J Lipid Res 2019 Feb 19. Epub 2019 Feb 19.

University of Groningen, Netherlands

Activation of macrophage inflammasomes leads to interleukin (IL)-1b and IL-18 secretion and promotes atherosclerosis and its complications in mice and humans. However, the specific role and underlying mechanisms of the inflammasome in atherogenesis are topics of active research. Several studies in hyperlipidemic mouse models found that the NLRP3 inflammasome contributes to atherosclerosis, but recent work suggests that a second hit, such as defective cholesterol efflux or accumulation of oxidized mitochondrial DNA, may be required for significant inflammasome activation. Read More

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http://dx.doi.org/10.1194/jlr.S091280DOI Listing
February 2019

Niacin: an old lipid drug in a new NAD+ dress.

J Lipid Res 2019 Feb 19. Epub 2019 Feb 19.

Ecole Polytechnique Federale de Lausanne, Switzerland

Niacin, the first anti-dyslipidemic drug, has been at the centerstage of lipid research for many decades before the discovery of statins. However, to date, despite its remarkable effects on lipid profiles, the clinical outcomes of niacin treatment on cardiac events is still debated. In addition to its historically well-defined interactions with central players of lipid metabolism, niacin can be processed by eukaryotic cells to synthesize a crucial cofactor, nicotinamide adenine dinucleotide (NAD+). Read More

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http://dx.doi.org/10.1194/jlr.S092007DOI Listing
February 2019

Rosiglitazone remodels the lipid droplets and britens human visceral and subcutaneous adipocytes ex vivo.

J Lipid Res 2019 Feb 19. Epub 2019 Feb 19.

Icahn School of Medicine at Mount Sinai, United States.

Treatment with PPARγ agonists in vivo improves human adipocyte metabolism, but the cellular mechanisms and possible depot differences in responsiveness to their effects are poorly understood. To examine the ex vivo metabolic effects of rosiglitazone, we cultured explants of human visceral (omental) and abdominal subcutaneous adipose tissues for 7 days. Rosiglitazone increased mRNA levels of transcriptional regulators of brite/beige adipocytes (PGC1α, PRDM16), triglyceride synthesis (GPAT3, DGAT1), and lipolysis (ATGL), similarly in adipose tissues from both depots. Read More

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http://dx.doi.org/10.1194/jlr.M091173DOI Listing
February 2019

For the sake of science.

J Lipid Res 2019 Feb 13. Epub 2019 Feb 13.

UCSF, United States.

N/A. Read More

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http://dx.doi.org/10.1194/jlr.E093245DOI Listing
February 2019

Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulation.

J Lipid Res 2019 Feb 8. Epub 2019 Feb 8.

University of Alberta, Canada;

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. TG accumulation in liver is a hallmark of NAFLD. Metabolic studies have confirmed that increased hepatic de novo lipogenesis in humans contributes to fat accumulation in the liver and to NAFLD progression. Read More

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http://dx.doi.org/10.1194/jlr.M092544DOI Listing
February 2019
1 Read

Fructose-induced hypertriglyceridemia in rhesus macaques is attenuated with fish oil or apoC3 RNA interference.

J Lipid Res 2019 Feb 5. Epub 2019 Feb 5.

UC Davis, United States;

Dyslipidemia and insulin resistance are significant adverse outcomes of consuming high-sugar diets. Conversely, dietary fish oil reduces plasma lipids. Diet-induced dyslipidemia in a rhesus model better approximates the pathophysiology of human metabolic syndrome than rodent models. Read More

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http://dx.doi.org/10.1194/jlr.M089508DOI Listing
February 2019
7 Reads

Simultaneous LC-MS/MS quantification of eight apolipoproteins in normal and hypercholesterolemic mouse plasma.

J Lipid Res 2019 Feb 5. Epub 2019 Feb 5.

University of Regensburg, Germany

Apolipoproteins are major structural and functional constituents of lipoprotein particles. As modulators of lipid metabolism, adipose tissue biology, and energy homeostasis, apolipoproteins may serve as biomarkers or potential therapeutic targets for cardiometabolic diseases. Mice are the preferred model to study metabolic and cardiovascular disease, but a comprehensive method to quantify circulating apolipoproteins in mice is lacking. Read More

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http://dx.doi.org/10.1194/jlr.D084301DOI Listing
February 2019
1 Read

Intramuscular adipocytes: a buried adipose tissue depot deserving more exploration.

J Lipid Res 2019 Feb 4. Epub 2019 Feb 4.

University of Wisconsin, United States

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http://dx.doi.org/10.1194/jlr.C093047DOI Listing
February 2019
1 Read

Treating cancer with phosphatidylinositol-3-kinase inhibitors: increasing efficacy and overcoming resistance.

J Lipid Res 2019 Feb 4. Epub 2019 Feb 4.

Weill Cornell Medicine, United States.

The discovery of the phosphatidylinositol-3-kinase (PI3K) pathway was a major advance in understanding growth factor signaling. The high frequency of PI3K pathway mutations in many cancers has encouraged a new field targeting cancer driver mutations. Although there have been many successes, targeting PI3K itself has proven challenging, in part because of its multiple isoforms with distinct roles. Read More

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http://dx.doi.org/10.1194/jlr.S092130DOI Listing
February 2019

Cyclodextrin triggers MCOLN1-dependent endo-lysosome secretion in Niemann-Pick type C cells.

J Lipid Res 2019 Feb 1. Epub 2019 Feb 1.

University of Geneva, Switzerland;

In specialized cell types, lysosome-related organelles support regulated secretory pathways, while in non-specialized cells, lysosomes can undergo fusion with the plasma membrane in response to a transient rise in cytosolic calcium. Recent evidence also indicates that lysosome secretion can be controlled transcriptionally and promote clearance in lysosome storage diseases. In addition, evidence is also accumulating that low concentrations of cyclodextrins reduce the cholesterol storage phenotype in cells and animals with the cholesterol storage disease Niemann-Pick type C, via an unknown mechanism. Read More

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http://dx.doi.org/10.1194/jlr.M089979DOI Listing
February 2019
1 Read

Repression of hepatocyte nuclear factor 4 alpha by AP-1 underlies dyslipidemia associated with retinoic acid.

J Lipid Res 2019 Feb 1. Epub 2019 Feb 1.

University of Illinois at Chicago, United States;

All- retinoic acid (atRA) is used to treat certain cancers or dermatologic diseases. A common adverse effect of atRA is hypercholesterolemia; cytochrome P450 (CYP) 7A repression is suggested as a driver. However, the underlying molecular mechanisms remain unclear. Read More

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http://dx.doi.org/10.1194/jlr.M088880DOI Listing
February 2019

Adipokine FABP4 integrates energy stores and counter regulatory metabolic responses.

J Lipid Res 2019 Jan 30. Epub 2019 Jan 30.

Harvard School of Public Health, United States

While counter regulatory hormones and mediators of the fight-or-flight responses are well defined at many levels, how energy stores per-se are integrated into this system remains an enigmatic question. Recent years have seen the adipose tissue become a central focus for mediating intracellular signaling and communication through the release of a variety of bioactive lipids and substrates, as well as various adipokines. A critical integration node among these mediators and responses is controlled by fatty acid binding protein 4 (FABP4), also known as adipocyte protein 2 (aP2), which is highly expressed in adipose tissue and functions as a lipid chaperone protein. Read More

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http://www.jlr.org/lookup/doi/10.1194/jlr.S091793
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http://dx.doi.org/10.1194/jlr.S091793DOI Listing
January 2019
2 Reads
4.421 Impact Factor

LC-MS/MS analyses of open flow microperfusion samples quantify eicosanoids in a rat model of skin inflammation.

J Lipid Res 2019 Jan 29. Epub 2019 Jan 29.

Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft mbH, Austria;

Eicosanoids are lipid mediator molecules with key roles in inflammatory skin diseases such as psoriasis. Eicosanoids are released close to the source of inflammation where they elicit local, pleiotropic effects and dysregulations. Monitoring inflammatory mediators directly in skin lesions could provide new insights and new therapeutic possibilities. Read More

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http://dx.doi.org/10.1194/jlr.M087221DOI Listing
January 2019

Lysophosphatidic acid type 2 receptor agonists in targeted drug development offer broad therapeutic potential.

J Lipid Res 2019 Jan 28. Epub 2019 Jan 28.

RxBio Inc., United States.

The growth factor-like lipid mediator lysophosphatidic acid (LPA) is a potent signaling molecule that influences numerous physiologic and pathologic processes. Manipulation of LPA signaling is of growing pharmacotherapeutic interest, especially because LPA resembles compounds with drug-like features. LPA action is mediated through activation of multiple types of molecular targets including six G-protein-coupled receptors - clear targets for drug development. Read More

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http://dx.doi.org/10.1194/jlr.S091744DOI Listing
January 2019

On the mechanism of angiopoietin-like protein 8 for control of lipoprotein lipase activity.

J Lipid Res 2019 Jan 27. Epub 2019 Jan 27.

Umea University, Sweden;

Angiopoietin-like (ANGPTL) 8 is a secreted inhibitor of lipoprotein lipase (LPL), a key enzyme in plasma triglyceride metabolism. It was previously reported that ANGPTL8 requires another member of the ANGPTL family, ANGPTL3, to act on lipoprotein lipase. ANGPTL3, much like ANGPTL4, is a physiologically relevant regulator of LPL activity, which causes irreversible inactivation of the enzyme. Read More

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http://dx.doi.org/10.1194/jlr.M088807DOI Listing
January 2019

It takes a village: channeling fatty acid metabolism and triacylglycerol formation via protein interactomes.

J Lipid Res 2019 Jan 25. Epub 2019 Jan 25.

University of North Carolina at Chapel Hill; School of Public Health, United States

Diet, hormones, gene transcription, and post-translational modifications control the hepatic metabolism of FAs; metabolic dysregulation causes chronic diseases, including cardiovascular disease, and warrants exploration into the mechanisms directing FA and triacylglycerol (TAG) synthesis and degradation. Long-chain FA metabolism begins by formation of an acyl-CoA by a member of the acyl-CoA synthetase family (ACSL). Subsequently, TAG synthesis begins with acyl-CoA esterification to glycerol-3-phosphate by a member of the glycerol-3-phosphate acyltransferase (GPAT) family. Read More

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http://dx.doi.org/10.1194/jlr.S091843DOI Listing
January 2019

A Perilous Path: The Inborn Errors of Sphingolipid Metabolism.

J Lipid Res 2019 Jan 25. Epub 2019 Jan 25.

National Institute of Diabetes and Digestive and Kidney Diseases/NIH, United States

The sphingolipid (SL) metabolic pathway generates structurally diverse lipids that have roles as membrane constituents and as bioactive signaling molecules. The influence of the SL metabolic pathway in biology is pervasive; it exists in all mammalian cells and has roles in many cellular and physiological pathways. Human genetic diseases have long been recognized to be caused by mutations in the pathway, but until recently these mutational defects were only known to affect lysosomal SL degradation. Read More

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http://www.jlr.org/lookup/doi/10.1194/jlr.S091827
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http://dx.doi.org/10.1194/jlr.S091827DOI Listing
January 2019
4 Reads

Therapeutic FGF19 promotes HDL biogenesis and transhepatic cholesterol efflux to prevent atherosclerosis.

J Lipid Res 2019 Jan 24. Epub 2019 Jan 24.

NGM Biopharmaceuticals, United States

FGF19, an endocrine hormone produced in the gut, acts in the liver to control bile acid synthesis. NGM282, an engineered FGF19 analogue, is currently in clinical development for treating non-alcoholic steatohepatitis. However, the molecular mechanisms that integrate FGF19 with cholesterol metabolic pathways are incompletely understood. Read More

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http://dx.doi.org/10.1194/jlr.M089961DOI Listing
January 2019
1 Read

Hepatocyte Sortilin 1 knockout and treatment with a Sortilin 1 inhibitor reduced plasma cholesterol in Western diet-fed mice.

J Lipid Res 2019 Jan 22. Epub 2019 Jan 22.

University of Kansas Medical Center, United States

Sortilin 1 (Sort1) is a member of the Vps10p domain intracellular trafficking receptor family. Genetic variations of SORT1 gene is strongly associated with plasma cholesterol levels in humans. Recent studies have linked Sort1 to regulation of cholesterol metabolism in hepatocytes and pro-inflammatory response in macrophages, but tissue-specific roles of Sort1 in lipid metabolism have not been well defined. Read More

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http://dx.doi.org/10.1194/jlr.M089789DOI Listing
January 2019
1 Read

A New LC-MS Assay for the Quantitative Analysis of Vitamin K Metabolites in Human Urine.

J Lipid Res 2019 Jan 22. Epub 2019 Jan 22.

University of Washington, United States.

Vitamin K, in both its phylloquinone and menaquinone forms, has been hypothesized to undergo ω- and β-oxidation on its hydrophobic side chain in order to generate the observed urinary metabolites, K Acid I and K Acid II, which are excreted primarily as glucuronide conjugates. Synthetic standards of K Acid I, K Acid II and a putative intermediate metabolite, MK1 ω-COOH, were used to develop and optimize a new APCI- LC-MS/MS assay for the quantitation of these compounds in urine from untreated individuals and subjects treated with a high dose vitamin K supplement. Vitamin K catabolites were extracted from urine, deconjugated and converted to their methyl ester derivatives using previously reported methodology. Read More

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http://dx.doi.org/10.1194/jlr.D087916DOI Listing
January 2019

Acid sphingomyelinase deficiency protects mitochondria and improves function recovery after brain injury.

J Lipid Res 2019 Jan 20. Epub 2019 Jan 20.

Medical University of South Carolina, United States

Traumatic brain injury (TBI) is one of the leading causes of disability worldwide and a prominent risk factor for neurodegenerative diseases. The expansion of nervous tissue damage after the initial trauma involves a multifactorial cascade of events including excitotoxicity, oxidative stress, inflammation and deregulation of sphingolipid metabolism that further mitochondrial dysfunction and secondary brain damage. Here, we show a post-transcriptional activation of an acid sphingomyelinase (ASM), a key enzyme of the sphingolipid recycling pathway, resulted in a selective increase of sphingosine in mitochondria during the first week post-TBI that was accompanied by reduced activity of mitochondrial cytochrome oxidase and activation of the NLRP3 inflammasome. Read More

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http://www.jlr.org/lookup/doi/10.1194/jlr.M091132
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http://dx.doi.org/10.1194/jlr.M091132DOI Listing
January 2019
2 Reads

CD36 plays a negative role in the regulation of lipophagy in hepatocytes through an AMPK-dependent pathway.

J Lipid Res 2019 Jan 20. Epub 2019 Jan 20.

Royal Free Campus, University College London, United Kingdom.

Fatty acid translocase CD36 (CD36) is a multifunctional membrane protein that facilitates the uptake of long-chain fatty acid (LCFA). Lipophagy is autophagic degradation of lipid droplets. Accumulating evidence suggests that CD36 is involved in the regulation of intracellular signal transduction that modulates fatty acid storage or usage. Read More

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http://www.jlr.org/lookup/doi/10.1194/jlr.M090969
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http://dx.doi.org/10.1194/jlr.M090969DOI Listing
January 2019
4 Reads
4.421 Impact Factor

Regulation of ABCA1-mediated cholesterol efflux by sphingosine-1-phosphate signalling in macrophages.

J Lipid Res 2019 Jan 17. Epub 2019 Jan 17.

University Hospital Essen, Germany;

Sphingolipid and cholesterol metabolism are closely associated at the structural, biochemical and functional levels. Although HDL-associated sphingosine-1-phosphate (S1P) contributes to several HDL functions, and S1P signaling regulates glucose and lipid metabolism, no study has addressed the involvement of S1P in cholesterol efflux. Here, we show that sphingosine kinase (Sphk) activity was induced by the LXR agonist 22(R)-hydroxycholesterol and required for the stimulation of ABCA1-mediated cholesterol efflux to apolipoprotein A-I. Read More

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http://dx.doi.org/10.1194/jlr.M088443DOI Listing
January 2019

New insights into functions of the sphingosine-1-phosphate transporter SPNS2.

J Lipid Res 2019 Jan 17. Epub 2019 Jan 17.

VCU School of Medicine, United States.

Sphingosine-1-phosphate (S1P) is a potent bioactive signaling molecule that regulates many physiological processes important for development, epithelial and endothelial barrier integrity, and the immune system, as well as for pathologies, such as autoimmune diseases, cancer, and metastasis. Most of the well-known actions of S1P are mediated by five specific G protein-coupled receptors located on the plasma membrane. Because S1P is synthesized intracellularly by two sphingosine kinase isoenzymes, we have proposed the paradigm of inside-out signaling by S1P, suggesting that S1P must be exported out of cells to interact with its receptors. Read More

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http://dx.doi.org/10.1194/jlr.S091959DOI Listing
January 2019

ACBD6 protein controls acyl chain availability and specificity of the N-myristoylation modification of proteins.

J Lipid Res 2019 Jan 14. Epub 2019 Jan 14.

Children s Hospital Oakland Research Institute, United States.

Members of the human acyl-CoA binding ACBD family regulate processes as diverse as viral replication, stem-cell self-renewal, organelle organization, and protein acylation. These functions are defined by non-conserved motifs present downstream of the acyl-CoA binding domain. The human ankyrin-repeat containing ACBD6 protein supports the reaction catalyzed by the human and Plasmodium N-myristoyl-transferase NMT enzymes. Read More

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http://dx.doi.org/10.1194/jlr.M091397DOI Listing
January 2019
1 Read

Longitudinal Lipid Trends and Adverse Outcomes in Patients with Chronic Kidney Disease: A 13-Year Observational Cohort Study Using Registry-Based Electronic Medical Records.

J Lipid Res 2019 Jan 14. Epub 2019 Jan 14.

China Medical University, Taiwan;

Studies on the effects of longitudinal lipid trajectories on end-stage renal disease(ESRD) development and deaths among patients with chronic kidney disease(CKD) are limited. We conducted a registry-based prospective study using data from a 13-year multidisciplinary pre-ESRD care program. The final study population comprised 4, 647 patients with CKD aged 20-90 years. Read More

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http://www.jlr.org/lookup/doi/10.1194/jlr.P084590
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http://dx.doi.org/10.1194/jlr.P084590DOI Listing
January 2019
6 Reads

Fifty years of lyase and a moment of truth: Sphingosine phosphate lyase from discovery to disease.

Authors:
Julie D Saba

J Lipid Res 2019 Jan 11. Epub 2019 Jan 11.

UCSF Benioff Children's Hospital Oakland, United States

Sphingosine phosphate lyase (SPL) is the final enzyme in the sphingolipid degradative pathway, catalyzing the irreversible cleavage of long chain base phosphates (LCBPs) to yield a long chain aldehyde and ethanolamine phosphate (EP). SPL guards the sole exit point of sphingolipid metabolism. Its inactivation causes product depletion and accumulation of upstream sphingolipid intermediates. Read More

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http://dx.doi.org/10.1194/jlr.S091181DOI Listing
January 2019
1 Read

A large scale high throughput screen identifies chemical inhibitors of phosphatidylinositol 4-kinase type II alpha.

J Lipid Res 2019 Jan 9. Epub 2019 Jan 9.

NIH, United States;

The minor phospholipid, phosphatidylinositol 4-phosphate (PI4P) is emerging as a key regulator of lipid transfer in ER-membrane contact sites. Four different phosphatidylinositol 4-kinase (PI4K) enzymes generate PI4P in different membrane compartments supporting distinct cellular processes, many of which are crucial for the maintenance of cellular integrity but also hijacked by intracellular pathogens. While type III PI4Ks have been targeted by small molecular inhibitors, thus helping decipher their importance in cellular physiology, no inhibitors are available for the type II PI4Ks, which hinders investigations into their cellular functions. Read More

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http://dx.doi.org/10.1194/jlr.D090159DOI Listing
January 2019

Polyunsaturated fatty acid metabolites: biosynthesis in Leishmania and role in parasite/host interaction.

J Lipid Res 2019 Jan 9. Epub 2019 Jan 9.

IRSD, INSERM, INRA, INP-ENVT, France;

Inside the human host, Leishmania infection starts with phagocytosis of infective promastigotes by macrophages. In order to survive, Leishmania has developed several strategies to manipulate macrophages function, among them the implication of bioactive lipids has been poorly explored. Herein, we assessed the biosynthesis of polyunsaturated fatty acid metabolites by infective and non-infective stages of Leishmania and further explored the role of these metabolites in macrophage polarization. Read More

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http://dx.doi.org/10.1194/jlr.M091736DOI Listing
January 2019

Genetic control of the mouse HDL proteome defines HDL traits, function, and heterogeneity.

J Lipid Res 2019 Jan 8. Epub 2019 Jan 8.

UCLA, United States.

High-density lipoproteins (HDL) are nanoparticles with more than 80 associated proteins, phospholipids, cholesterol and cholesteryl esters. A comprehensive genetic analysis of the regulation of proteome of HDL isolated from a panel of 100 diverse inbred strains of mice, Hybrid Mouse Diversity Panel (HMDP), revealed widely varied HDL protein levels across the strains. Some of this variation was explained by local, cis-acting regulation, termed cis-protein quantitative trait loci. Read More

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http://dx.doi.org/10.1194/jlr.M090555DOI Listing
January 2019

Unequivocal evidence for endogenous geranylgeranoic acid biosynthesized from mevalonate in mammalian cells.

J Lipid Res 2019 Jan 8. Epub 2019 Jan 8.

University of Nagasaki, Japan.

Geranylgeranoic acid (GGA) has been reported to induce autophagic cell death via upregulation of lipid-induced unfolded protein response in several human hepatoma-derived cell lines, and its 4,5-didehydro derivative has been developed as a preventive agent against second primary hepatoma in clinical trials. We have previously reported that GGA is a natural diterpenoid synthesized in several medicinal herbs. Here, we provide unequivocal evidence for de novo GGA biosynthesis in mammals. Read More

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http://dx.doi.org/10.1194/jlr.M090548DOI Listing
January 2019
4.421 Impact Factor

Systems-based approaches for investigation of inter-tissue communication.

J Lipid Res 2019 Jan 7. Epub 2019 Jan 7.

UCLA, United States

Secreted proteins serve as crucial mediators of many physiology processes, and beginning with the discovery of insulin, studies have revealed numerous context-specific regulatory networks across various cell types. Here, we review omics approaches to deconvolute the complex milieu of proteins which are released from the cell. We emphasize a novel systems genetics approach our lab has developed to investigate mechanisms of tissue-tissue communication using population-based datasets. Read More

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http://dx.doi.org/10.1194/jlr.S090316DOI Listing
January 2019

Identification of amino acid residues in the ligand binding repeats of LDLR important for PCSK9 binding.

J Lipid Res 2019 Jan 7. Epub 2019 Jan 7.

University of Alberta, Canada;

Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes LDL receptor (LDLR) degradation, increasing plasma levels of LDL cholesterol and the risk of cardiovascular disease. We have previously shown that, in addition to the epidermal growth factor precursor homology repeat-A of LDLR, at least three ligand-binding repeats (LRs) of LDLR are required for PCSK9-promoted LDLR degradation. However, how exactly the LRs contribute to PCSK9's action on the receptor is not completely understood. Read More

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http://dx.doi.org/10.1194/jlr.M089193DOI Listing
January 2019
1 Read

Synthesis and characterization of diazirine alkyne probes for the study of intracellular cholesterol trafficking.

J Lipid Res 2019 Jan 7. Epub 2019 Jan 7.

Washington University, United States

Cholesterol is an essential structural component of cellular membranes and precursor molecule for oxysterol, bile acid, and hormone synthesis. The study of intracellular cholesterol trafficking pathways has been limited in part due to a lack of suitable cholesterol analogs. Herein, we developed three novel diazirine alkyne cholesterol probes LKM38, KK174, and KK175. Read More

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http://www.jlr.org/lookup/doi/10.1194/jlr.D091470
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http://dx.doi.org/10.1194/jlr.D091470DOI Listing
January 2019
17 Reads

Three Phase Liquid Extraction (3PLE): A Simple, and Fast Method for Lipidomic Workflows.

J Lipid Res 2019 Jan 4. Epub 2019 Jan 4.

Southwestern Medical Center, United States

Unbiased sample preparation free of interferents (i.e., competing analytes, detergents, plastics) is critical to any lipid mass spectrometry (MS) workflow. Read More

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http://www.jlr.org/lookup/doi/10.1194/jlr.D090795
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http://dx.doi.org/10.1194/jlr.D090795DOI Listing
January 2019
7 Reads

Gallbladder bile supersaturated with cholesterol in gallstone patients preferentially develops from shortage of bile acids.

J Lipid Res 2019 Jan 4. Epub 2019 Jan 4.

Karolinska Institutet, Sweden.

Gallstone formation requires that bile is supersaturated with cholesterol, estimated by a cholesterol saturation index (CSI) calculated from gallbladder total lipids and the mol % bile acids, cholesterol and phospholipids. Whereas CSI indicates gallstone risk, we hypothesized that additional comparisons of gallbladder lipid mol % data are inappropriate to identify why CSI is increased in gallstone disease. We anticipated gallbladder lipid mmol/L levels should instead identify that and therefore retrieved gallbladder mmol/L data for bile acids, cholesterol and phospholipids from a study on 145 gallstone and 87 gallstone-free patients and compared them with the corresponding mol % data. Read More

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http://dx.doi.org/10.1194/jlr.S091199DOI Listing
January 2019

Hepatic Monoacylglycerol Acyltransferase 1 is Induced by Prolonged Food Deprivation to Modulate the Hepatic Fasting Response.

J Lipid Res 2019 Jan 4. Epub 2019 Jan 4.

Washington University School of Medicine, United States;

During prolonged fasting, the liver plays a central role in maintaining systemic energy homeostasis by producing glucose and ketones in processes fueled by oxidation of fatty acids liberated from adipose tissue. In mice, this is accompanied by transient hepatic accumulation of glycerolipids. We found that the hepatic expression of monoacylglycerol acyltransferase 1 (Mogat1), an enzyme with monoacylglycerol acyltransferase (MGAT) activity that produces diacylglycerol from monoacylglycerol, was significantly increased in liver of fasted mice compared to mice given ad libitum access to food. Read More

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http://dx.doi.org/10.1194/jlr.M089722DOI Listing
January 2019

Lysophospholipid acyltransferases and leukotriene biosynthesis: intersection of the Lands cycle and the arachidonate PI cycle.

J Lipid Res 2019 Feb 3;60(2):219-226. Epub 2019 Jan 3.

Department of Pharmacology, University of Colorado Denver, Aurora, CO 80045.

Leukotrienes (LTs) are autacoids derived from the precursor arachidonic acid (AA) via the action of five-lipoxygenase (5-LO). When inflammatory cells are activated, 5-LO translocates to the nuclear membrane to initiate oxygenation of AA released by cytosolic phospholipase A2 (cPLA2) into leukotriene A (LTA). LTA can also be exported from an activated donor cell into an acceptor cell by the process of transcellular biosynthesis. Read More

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http://dx.doi.org/10.1194/jlr.S091371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358305PMC
February 2019

An upstream enhancer regulates expression in a tissue-specific manner.

J Lipid Res 2018 Dec 31. Epub 2018 Dec 31.

University of California, Los Angeles, United States;

GPIHBP1, the protein that shuttles lipoprotein lipase (LPL) to the capillary lumen, is essential for plasma triglyceride metabolism. When GPIHBP1 is absent, LPL remains stranded within the interstitial spaces and plasma triglyceride hydrolysis is impaired, resulting in severe hypertriglyceridemia. While the functions of GPIHBP1 in intravascular lipolysis are reasonably well understood, no one has yet identified DNA sequences regulating GPIHBP1 expression. Read More

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http://www.jlr.org/lookup/doi/10.1194/jlr.M091322
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http://dx.doi.org/10.1194/jlr.M091322DOI Listing
December 2018
10 Reads

Cerebral gustatory activation in response to free fatty acids using gustatory evoked potentials in humans.

J Lipid Res 2018 Dec 26. Epub 2018 Dec 26.

Universite Bourgogne, France

There is some evidence of specific oro-detection of free fatty acids (FFA) in rodents and humans. The aim of this study was to record gustatory evoked potentials (GEPs) in response to FFA solutions, and to compare GEPs in response to linoleic acid solution with GEPs obtained after stimulation with sweet and salty tastants. Eighteen healthy men were randomly stimulated with fatty (linoleic acid), sweet (sucrose) and salty (NaCl) solutions, at two concentrations in the first experiment. Read More

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http://dx.doi.org/10.1194/jlr.M086587DOI Listing
December 2018
1 Read

Docosahexaenoic acid is both a product of and a precursor to tetracosahexaenoic acid in the rat.

J Lipid Res 2019 Feb 20;60(2):412-420. Epub 2018 Dec 20.

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

Tetracosahexaeoic acid (THA; 24:6n-3) is thought to be the immediate precursor of DHA in rodents; however, the relationship between THA and DHA metabolism has not been assessed in vivo. Here, we infused unesterified H-THA and C-DHA, at a steady state, into two groups of male Long-Evans rats and determined the synthesis-secretion kinetics, including daily synthesis-secretion rates of all 20-24 carbon n-3 PUFAs. We determined that the synthesis-secretion coefficient (a measure of the capacity to synthesize a given fatty acid) for the synthesis of DHA from plasma unesterified THA to be 134-fold higher than for THA from DHA. Read More

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http://dx.doi.org/10.1194/jlr.M090373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358307PMC
February 2019

Flux analysis reveals regulation of the sphingolipid network by doxorubicin in breast cancer cells.

J Lipid Res 2018 Dec 20. Epub 2018 Dec 20.

Stony Brook University, United States

Sphingolipids (SLs) are implicated in numerous important cellular biologies, from proliferation to apoptosis. SL function in cancer cells has spurred interest in their modulation for cancer therapies; however, study is hindered by the complexities of SL metabolism. Enzymes of SL metabolism represent a dynamic, interconnected network in which one metabolite can be transformed into other bioactive SLs, resulting in diverse cellular responses. Read More

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http://www.jlr.org/lookup/doi/10.1194/jlr.M089714
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http://dx.doi.org/10.1194/jlr.M089714DOI Listing
December 2018
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A monoclonal antibody to assess oxidized cholesteryl esters associated with apoAI and apoB-100 lipoproteins in human plasma.

J Lipid Res 2019 Feb 18;60(2):436-445. Epub 2018 Dec 18.

Department of Medicine, University of California, San Diego, La Jolla, CA 92093

Atherosclerosis is associated with increased lipid peroxidation, leading to generation of multiple oxidation-specific epitopes (OSEs), contributing to the pathogenesis of atherosclerosis and its clinical manifestation. Oxidized cholesteryl esters (OxCEs) are a major class of OSEs found in human plasma and atherosclerotic tissue. To evaluate OxCEs as a candidate biomarker, we generated a novel mouse monoclonal Ab (mAb) specific to an OxCE modification of proteins. Read More

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http://dx.doi.org/10.1194/jlr.D090852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358287PMC
February 2019

The structure of human apolipoprotein C-1 in four different crystal forms.

J Lipid Res 2019 Feb 17;60(2):400-411. Epub 2018 Dec 17.

Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697-3900.

Human apolipoprotein C1 (APOC1) is a 57 amino acid long polypeptide that, through its potent inhibition of cholesteryl ester transferase protein, helps regulate the transfer of lipids between lipid particles. We have now determined the structure of APOC1 in four crystal forms by X-ray diffraction. A molecule of APOC1 is a single, slightly bent, α-helix having 13-14 turns and a length of about 80 Å. Read More

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http://dx.doi.org/10.1194/jlr.M089441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358290PMC
February 2019

Melatonin reduces intramuscular fat deposition by promoting lipolysis and increasing mitochondrial function.

J Lipid Res 2018 Dec 14. Epub 2018 Dec 14.

Nanjing Agricultural University, China

In obesity and diabetes, intramuscular fat (IMF) content correlates markedly with insulin sensitivity, which makes IMF manipulation an area of therapeutic interest. Melatonin, an important circadian rhythm-regulating hormone, reportedly regulates fat deposition, but its effects on different types of adipose vary. Little is known about the role of melatonin in IMF deposition. Read More

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http://dx.doi.org/10.1194/jlr.M087619DOI Listing
December 2018
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Erythrocyte PUFAs, circulating acylcarnitines, and metabolic syndrome risk: a prospective study in Chinese.

J Lipid Res 2019 Feb 14;60(2):421-429. Epub 2018 Dec 14.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Chinese Academy of Sciences, Shanghai 200031, China

The effects of PUFAs on metabolic syndrome (MetS) remain to be characterized, particularly in Asians. We aimed to investigate the prospective associations of PUFAs with MetS and the role of acylcarnitines in these associations in Chinese individuals. Among 1,245 Chinese men and women aged 50-70 years who completed a 6 year follow-up, baseline erythrocyte FAs and plasma acylcarnitines were profiled using gas chromatography coupled with positive chemical ionization and liquid chromatography-tandem mass spectrometry, respectively. Read More

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http://dx.doi.org/10.1194/jlr.P088005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358288PMC
February 2019
1 Read
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Sphingoid bases of dietary ceramide 2-aminoethylphosphonate, a marine sphingolipid, absorb into lymph in rats.

J Lipid Res 2019 Feb 14;60(2):333-340. Epub 2018 Dec 14.

Laboratory of Technology of Marine Bioproducts, Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawaoiwakecho, Sakyo-ku, Kyoto 606-8502, Japan

Various functions of dietary sphingolipids have been reported; however, little is known about marine sphingolipids. Ceramide 2-aminoethylphosphonate (CAEP), an abundant sphingolipid in marine mollusks, frequently has a unique triene type of sphingoid base [2-amino-9-methyl-4,8,10-octadecatriene-1,3-diol (d19:3)]. We previously reported that dietary CAEP prepared from the skin of squid was digested in the intestinal mucosa of mice via ceramides to yield free sphingoid bases. Read More

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http://dx.doi.org/10.1194/jlr.M085654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358292PMC
February 2019
1 Read