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Journal of Lipid Research

Amy E Rumora, Giovanni LoGrasso, Julia A Haidar, Justin J Dolkowski, Stephen I Lentz, Eva L Feldman
Dyslipidemia associated with T2D leads to diabetic neuropathy, a complication characterized by sensory neuronal dysfunction and peripheral nerve damage. Sensory dorsal root ganglion (DRG) neurons are dependent on axonal mitochondrial energy production facilitated by mitochondrial transport mechanisms that distribute mitochondria throughout the axon. Since long chain saturated fatty acids (SFAs) damage DRG neurons and medium chain SFAs are reported to improve neuronal function, we evaluated the impact of SFA chain length on mitochondrial trafficking, mitochondrial function, and apoptosis...
November 15, 2018: Journal of Lipid Research
Guido Baselli, Luca Valenti
No abstract text is available yet for this article.
November 12, 2018: Journal of Lipid Research
Anna N Bukiya, Paul S Blank, Avia Rosenhouse-Dantsker
Cholesterol, a critical component of the cellular plasma membrane, is essential for normal neuronal function. Cholesterol content is highest in the brain, where most cholesterol is synthesized de novo; HMG-CoA reductase controls the synthesis rate. Despite strict control, elevated blood cholesterol levels are common and are associated with various neurological disorders. G protein-gated inwardly rectifying potassium (GIRK) channels mediate the actions of inhibitory brain neurotransmitters. Loss of GIRK function enhances neuron excitability; gain of function reduces neuronal activity...
November 12, 2018: Journal of Lipid Research
Renxue Wang, Jonathan A Sheps, Lin Liu, Jun Han, Patrick S K Chen, Jason Lamontagne, Peter D Wilson, Ian D Welch, Christoph H Borchers, Victor Ling
Bile acid imbalance causes progressive familial intrahepatic cholestasis type 2 (PFIC2) or type 3 (PFIC3) - severe liver diseases associated with genetic defects in the biliary bile acid transporter BSEP (ABCB11), or phosphatidylcholine transporter MDR3 (ABCB4), respectively. Mdr2 -/- mice (a PFIC3 model) develop progressive cholangitis, ductular proliferation, periportal fibrosis, and hepatocellular carcinoma (HCC) because the non-micelle-bound bile acids in the bile of these mice are toxic. We asked whether the highly hydrophilic bile acids generated by Bsep -/- mice could protect Mdr2 -/- mice from progressive liver damage...
November 11, 2018: Journal of Lipid Research
Stefan Coassin, Sebastian Schoenherr, Hansi Weissensteiner, Gertraud Erhart, Lukas Forer, Jamie L Losso, Claudia Lamina, Margot Haun, Gerd Utermann, Bernhard Paulweber, Guenther Specht, Florian Kronenberg
Lipoprotein(a) concentrations are among the strongest genetic risk factors for cardiovascular disease and present pronounced inter-ethnic and inter-individual differences. About 90% of lipoprotein(a) variance is controlled by the LPA gene, which contains a 5.6 kb large copy number variation (KIV-2 repeat) that generates >40 protein isoforms. Variants within the KIV-2 region are not called in common sequencing projects, leaving up to 70% of the LPA coding region currently unaddressed. To allow a complete assessment of the variability in LPA, we developed a sequencing strategy for this region and report here the first map of genetic variation in the KIV-2 region, a comprehensively evaluated ultra-deep sequencing protocol and an easy-to-use variant analysis pipeline (https://github...
November 9, 2018: Journal of Lipid Research
Eriko Sugano, Genea Edwards, Saikat Saha, Lynda Wilmott, Richard C Grambergs, Koushik Mondal, Hui Qi, Megan Stiles, Hiroshi Tomita, Nawajes A Mandal
Over 11 million people in the United States alone have some form of age-related macular degeneration (AMD). Oxidative stress, cell death, and the degeneration of retinal pigment epithelial (RPE) cells contributes to AMD pathology. Recent evidence suggests that Ceramide (Cer), a cellular sphingolipid mediator that acts as a second messenger to induce apoptosis, might play a role in RPE cell death. The lysosomal breakdown of Cer by acid Ceramidase (ASAH1, N-acylsphingosine amidohydrolase 1) into sphingosine is the major source for sphingosine 1-phosphate (S1P) production, which has an opposing role to Cer and provides cytoprotection...
November 9, 2018: Journal of Lipid Research
Hongbin Xu, Frederic R Boucher, Thao T Nguyen, Graeme P Taylor, Julianna Tomlinson, Roberto A Ortega, Brigitte Simons, Michael Schlossmacher, Rachel Saunders-Pullman, Walt Shaw, Steffany A L Bennett
Cerebrosides, including glucosylceramides (GlcCer) and galactosylceramides (GalCer), are important membrane components of animal cells with deficiencies resulting in devastating lysosomal storage disorders. Their quantification is essential for disease diagnosis and a better understanding of disease mechanisms. Simultaneous quantification of GlcCer and GalCer isomers is, however, particularly challenging due to their virtually identical structures. To address this challenge, we developed a new LC-MS-based method employing differential ion mobility spectrometry (DMS) capable of rapidly and reproducibly separating and quantifying isomeric cerebrosides in a single run...
November 9, 2018: Journal of Lipid Research
Maximilian Blum, Inci Dogan, Mirjam Karber, Michael Rothe, Wolf-Hagen Schunck
A chiral lipidomics approach was established for comprehensive profiling of regio- and stereoisomeric monoepoxy and monohydroxy metabolites of long-chain polyunsaturated fatty acids as generated enzymatically by cytochromes P450, lipoxygenases, and cyclooxygenases and, in part, also unspecific oxidations. The method relies on reversed-phase chiral liquid chromatography coupled with electrospray ionization/tandem mass spectrometry. Applications revealed partially opposing enantioselectivities of soluble and microsomal epoxide hydrolases...
November 8, 2018: Journal of Lipid Research
Zehra Irshad, Nikola Chmel, Raghu Adya, Victor A Zammit
DGAT1 activity is expressed on both aspects of the endoplasmic reticulum (dual membrane-topology) and plays a distinctive role in determining the triglyceride (TAG) content of VLDL particles secreted by the liver. Mice specific DGAT1 ablation in hepatocytes (DGAT1-LKO mice) had the same number of VLDL particles (apoB concentration) in the plasma, but these particles were approximately halve the size of VLDL particles secreted by control mice, and had a proportionately decreased content of TAG, with normal cholesterol and cholesterol ester contents...
November 5, 2018: Journal of Lipid Research
Feroz Ahmad, David S Leake
Objective We have shown that aggregated low density lipoproteins (LDL) is internalised by macrophages and oxidised in lysosomes by redox-active iron. We have now investigated if the lysosomal oxidation of LDL impairs lysosomal function and if a lysosomotropic antioxidant can prevent these alterations. Approach and Results LDL aggregated by sphingomyelinase (SMase-LDL) caused increased lysosomal lipid peroxidation in human monocyte-derived macrophages or THP-1 macrophage-like cells, as shown by a fluorescent probe, Foam-LPO...
November 5, 2018: Journal of Lipid Research
Yohei Ohashi, Shirley Tremel, Roger L Williams
VPS34 phosphorylates phosphatidylinositol to produce PtdIns3P and is the progenitor of the PI3K family. VPS34 has a simpler domain organization than class I PI3Ks, which belies the complexity of its quaternary organization, with the enzyme always functioning within larger assemblies. PtdIns3P recruits specific recognition modules that are common in protein sorting pathways such as autophagy and endocytic sorting. It is best characterized in two heterotetramers, complexes I and II. Complex I is composed of VPS34, VPS15, Beclin 1, and ATG14L, whereas complex II replaces ATG14L with UVRAG...
November 5, 2018: Journal of Lipid Research
Xiaoyue Pan, Gary J Schwartz, M Mahmood Hussain
Dietary fat absorption takes place in the intestine, and the liver mobilizes endogenous fat to other tissues by synthesizing lipoproteins that requires apoB and microsomal TG transfer protein (MTP). Dietary fat triggers the synthesis of oleoylethanolamide (OEA) - a regulatory fatty acid that signals satiety to reduce food intake, mainly by enhancing neural PPARα activity - in enterocytes. We explored OEA roles in the assembly of lipoproteins in wild-type and Ppara-/- mouse enterocytes and hepatocytes, Caco-2 cells, and human liver-derived cells...
October 28, 2018: Journal of Lipid Research
Benedikt Kien, Susanne Grond, Guenter Haemmerle, Achim Lass, Thomas O Eichmann, Franz P W Radner
Mutations in the genes coding for patatin-like phospholipase domain-containing 1 (PNPLA1) and α/β-hydrolase domain-containing 5 (ABHD5), also known as comparative gene idenfication-58 (CGI-58), are causative for a severe skin barrier disorder, termed ichthyosis. Individuals with mutations in either of these genes show a defect in epidermal ω-O-acylceramide (AcylCer) biosynthesis, suggesting that PNPLA1 and ABHD5 act in the same metabolic pathway. In this report, we identified ABHD5 as a coactivator of PNPLA1 that stimulates the esterification of ω-hydroxy ceramides with linoleic acid for AcylCer biosynthesis...
October 25, 2018: Journal of Lipid Research
Patricia Vázquez, Catalina Hérnandez-Sánchez, Carmen Escalona-Garrido, Laura Pereira, Cristina Contreras, Miguel López, Jesús Balsinde, Flora de Pablo, Angela M Valverde
Tyrosine hydroxylase (TH) catalyzes the first step in catecholamines synthesis. We studied the impact of reduced TH in brown adipose tissue (BAT) activation. In adult heterozygous (Th+/-) mice, dopamine and noradrenaline (NA) content in BAT decreased after cold exposure. This reduced catecholaminergic response did not impair cold adaptation, since these mice induced uncoupling protein-1 (UCP1) and maintained BAT temperature to a similar extent than controls (Th+/+). Possible compensatory mechanisms implicated were studied...
October 23, 2018: Journal of Lipid Research
Takuya Takeichi, Yusuke Okuno, Akane Kawamoto, Takeshi Inoue, Eiko Nagamoto, Chiaki Murase, Eri Shimizu, Kenichi Tanaka, Yuichi Kageshita, Satoshi Fukushima, Michihiro Kono, Junko Ishikawa, Hironobu Ihn, Yoshiyuki Takahashi, Masashi Akiyama
Neu-Laxova syndrome (NLS) is a very rare autosomal recessive congenital disorder characterized by disturbed development of the central nervous system and the skin, caused by mutations in any of the three genes involved in de novo L-serine biosynthesis: PHGDH , PSAT1 and PSPH L-serine is essential for the biosynthesis of phosphatidylserine and sphingolipids. The extracellular lipid of the stratum corneum, of which sphingolipid constitutes a significant part, plays a primary role in the skin barrier function...
October 22, 2018: Journal of Lipid Research
Andrew S Geller, Eliana Y Polisecki, Margaret R Diffenderfer, Bela F Asztalos, Sotirios K Karathanasis, Robert A Hegele, Ernst J Schaefer
We assessed secondary and genetic causes of severe HDL deficiency in 258,252 subjects, of whom 370 men (0.33%) and 144 women (0.099%) had HDL-C levels <20 mg/dL. We excluded 206 subjects (40.1%) with significant elevations of triglycerides, C reactive protein, glycosylated hemoglobin, myeloperoxidase, or liver enzymes, and men receiving testosterone. We sequenced 23 lipid-related genes in 201 (65.3%) of 308 eligible subjects. Mutations (23 novel) and selected variants were found at the following gene loci: 1) ABCA1 (26...
October 17, 2018: Journal of Lipid Research
Aicha Saadane, Alexey Petrov, Natalia Mast, Nicole El-Darzi, Tung Dao, Ahab Alnemri, Ying Song, Joshua L Dunaief, Irina A Pikuleva
Apolipoprotein E (APOE) is a component of lipid-transporting particles and a recognition ligand for receptors, which bind these particles. The APOE isoform 2 is a risk factor for age-related macular degeneration; nevertheless APOE absence in humans and mice does not significantly affect the retina. We found that retinal cholesterol biosynthesis and the levels of retinal cholesterol were increased in Apoe-/- mice, whereas cholesterol elimination by metabolism was decreased. No focal cholesterol deposits were observed in the Apoe-/- retina...
October 17, 2018: Journal of Lipid Research
Charlotte M Beddoes, Gert S Gooris, Joke A Bouwstra
The lipid matrix of the stratum corneum - the outermost skin layer - consists primarily of ceramides, cholesterol, and free fatty acids (FFAs). These lipids form a trilayer long periodicity phase (LPP) that is unique to this barrier. Knowledge about the LPP is essential to understand the barrier function. Previous studies of LPP lipid models have identified the position of the major lipid classes and, suggested that a large fraction of FFAs and the ceramide acyl chain are present in the central region. However, the precise arrangement, such as lipid subclass mixing (isolated or mixed) and ceramide conformation (extended or hairpin) remains unknown...
October 17, 2018: Journal of Lipid Research
Carlos J Pirola, Martin Garaycoechea, Diego Flichman, Marco Arrese, Julio San Martino, Carla Gazzi, Gustavo O Casta Ntildeo, Silvia Sookoian
Hydroxysteroid 17βdehydrogenase 13 (HSD17B13) is a lipid droplet-associated protein; its gene-encoding variants affect the chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD). To estimate the effect of rs72613567, a splice variant with an adenine insertion (A-INS), on NAFLD susceptibility and severity, we performed a case-control study with 609 individuals. We investigated the effect of carrying the A-INS allele in 356 patients with biopsy-proven disease and explored the relationship between rs72613567genotypes and the hepatic transcriptome...
October 15, 2018: Journal of Lipid Research
Oswald Quehenberger, Signe Dahlberg-Wright, Jiang Jiang, Aaron M Armando, Edward A Dennis
Eicosanoids and related metabolites (oxylipins) possess potent signaling properties, elicit numerous important physiologic responses, and serve as biomarkers of disease. In addition to their presence in free form, a considerable portion of these bioactive lipids is esterified to complex lipids in cell membranes and plasma lipoproteins. We developed a rapid and sensitive method for the analysis of esterified oxylipins using alkaline hydrolysis to release them followed by ultra-performance liquid chromatography coupled with mass spectrometric analysis...
October 15, 2018: Journal of Lipid Research
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