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Journal of Lipid Research

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https://www.readbyqxmd.com/read/29150495/small-dense-high-density-lipoproteins-display-potent-vasorelaxing-activity-reflecting-their-elevated-content-of-sphingosine-1-phosphate
#1
Laurence Persegol, Maryam Darabi, Carolane Dauteuille, Marie Lhomme, Sandrine Chantepie, Kerry-Anne Rye, Patrice Therond, M John Chapman, Robert Salvayre, Anne Negre-Salvayre, Philippe Lesnik, Serge Monier, Anatol Kontush
AIMS: Functional heterogeneity of HDL is attributed to its diverse bioactive components. We evaluated whether vasodilatory effects of HDL differed across HDL subpopulations, reflecting their distinct molecular composition. METHODS: Capacity of five major HDL subfractions to counteract inhibitory effects of oxidized low-density lipoprotein on acetylcholine-induced vasodilation was tested in a rabbit aortic rings model. Nitric oxide (NO) production, an essential pathway in endothelium-dependent vasorelaxation, was studied in SV40-transformed murine endothelial cells (SVEC)...
November 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29133292/intracellular-hepatitis-b-virus-increases-hepatic-cholesterol-deposition-in-alcoholic-fatty-liver-via-hepatitis-b-core-protein
#2
Ya-Qi Wang, Ting Wu, Dan-Qing Hu, Xin-Xin Weng, Xiao-Jing Wang, Pei-Jer Chen, Xiao-Ping Luo, Hong-Wu Wang, Qin Ning
Hepatits B virus (HBV) infection is a prevalent infectious disease with serious outcomes like chronic and acute hepatitis, cirrhosis and hepatocellular carcinoma. However, the metabolic alteration by HBV is rarely taken into concerns. With the high prevalence of alcohol consumption and chronic HBV infection, their overlap is assumed as an increasing latent hazard although without exact calculation, moreover, the impact of chronic alcoholic consumption combined with HBV on cholesterol metabolism is unknown. Six-week-old male FVB/Ncrl mice were hydrodynamically injected with a pGEM-4Z-1...
November 13, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29122977/a%C3%AE-inhibits-srebp-2-activation-through-akt-inhibition
#3
Amany Mohamed, Anissa Viveiros, Kathleen Williams, Elena Posse de Chaves
We previously demonstrated that oligomeric Aβ42 (oAβ42 ) inhibits the mevalonate pathway impairing cholesterol synthesis and protein prenylation. Enzymes of the mevalonate pathway are regulated by the transcription factor sterol regulatory element binding protein (SREBP) 2. Here, we show that in several neuronal types challenged with o Aβ42, SREBP-2 activation is reduced. Moreover, SREBP-2 activation is also decreased in brain cortex of the Alzheimer's disease (AD) mouse model TgCRND8, suggesting that SREBP-2 may be affected in vivo during disease...
November 9, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29122890/microrna-30c-reduces-plasma-cholesterol-in-homozygous-familial-hypercholesterolemic-and-type-2-diabetic-mouse-models
#4
Sara Irani, Jahangir Iqbal, W James Antoni, Laraib Ijaz, M Mahmood Hussain
High plasma cholesterol levels are found in several metabolic disorders and their reductions are advocated to reduce risk of atherosclerosis. A way to lower plasma lipids is to curtail lipoprotein production; however, this is associated with steatosis. We previously showed that microRNA-30c (miR-30c) lowers diet-induced hypercholesterolemia and atherosclerosis in C57BL/6J and Apoe-/- mice. Here, we tested miR-30c effect on plasma lipids, transaminases and hepatic lipids in different mouse models. Hepatic delivery of miR-30c to chow fed leptin deficient (ob/ob) and leptin receptor deficient (db/db) hypercholesterolemic and hyperglycemic mice reduced cholesterol in total plasma and VLDL/LDL by ~28% and ~25%, respectively, without affecting triglyceride and glucose levels...
November 9, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29113994/hepatocyte-specific-deletion-of-bap31-promotes-srebp1c-activation-promotes-hepatic-lipid-accumulation-and-worsens-insulin-resistance-in-mice
#5
Jia-Lin Xu, Li-Ya Li, Yan-Qing Wang, Ya-Qi Li, Mu Shan, Shi-Zhuo Sun, Yang Yu, Bing Wang
Conditional knockout mice with targeted disruption of BAP31 in adult mouse liver were generated and challenged with a high-fat diet (HFD) for 36 or 96 days, markers of obesity, diabetes, and hepatic steatosis were determined. Mutant mice were indistinguishable from wild-type littermates, but exhibited increased HFD-induced obesity. BAP31-deletion in hepatocytes increased the expression of SREBP1C and the target genes, including ACC1 and SCD1, increased hepatic lipid accumulation and HFD-induced liver steatosis...
November 7, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29092960/quantification-of-3-ketodihydrosphingosine-using-hplc-esi-ms-ms-to-study-spt-activity-in-yeast-saccharomyces-cerevisiae
#6
Jihui Ren, Justin Snider, Michael V Airola, Aaron Zhong, Nadia A Rana, Lina M Obeid, Yusuf A Hannun
Serine palmitoyltransferase (SPT) catalyzes the rate-limiting step of condensation of L-serine and palmitoyl-CoA to form 3-ketodihydrosphingosine (3KDS). Here we report a HPLC-ESI-MS/MS method to directly quantify 3KDS generated by SPT. With this technique we were able to detect 3KDS at a level comparable to that of dihydrosphingosine (DHS) in yeast S.cerevisiae. An in vitro SPT assay measuring the incorporation of deuterated serine into deuterated 3KDS was developed. The results show that SPT kinetics in response to palmitoyl-CoA fit into an allosteric sigmoidal model, suggesting the existence of more than one palmitoyl-CoA binding site on yeast SPT and positive cooperativity between them...
November 1, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29092959/evidence-of-hydrocarbon-nanodrops-in-highly-ordered-stratum-corneum-model-membranes
#7
Adrian Paz Ramos, Gert Gooris, Joke Bouwstra, Michel Lafleur
The stratum corneum (SC), the top layer of skin, dictates both the rate of water loss through the skin, and absorption of exogenous molecules into the body. The crystalline organization of the lipids in the SC is believed to be a key feature associated with the very limited permeability of the skin. In this work, we characterized the organization of SC lipid models that include, as in native SC, cholesterol, a free fatty acid series (saturated with C16-C24 chains), as well as a ceramide bearing an oleate linked to a very long saturated acyl chain (Cer EOS)...
November 1, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29089366/macronutrient-specific-effect-of-the-mtnr1b-genotype-on-lipid-levels-in-response-to-2-year-weight-loss-diets
#8
Leticia Goni, Dianjianyi Sun, Yoriko Heianza, Tiange Wang, Tao Wang, Marta Cuervo, J Alfredo Martinez, Xiaoyun Shang, George A Bray, Frank M Sacks, Lu Qi
Compelling evidence indicates that lipid metabolism is into partly control of the circadian system. In this context, it has been reported that the Melatonin receptor 1B (MTNR1B) genetic variant influences the dynamics of melatonin secretion, which is involved in the circadian system as a chronobiotic. The objective was to analyze whether the MTNR1B rs10830963 genetic variant was related to changes in lipid levels in response to dietary interventions with different macronutrient distribution in 722 overweight/obese subjects from the POUNDS Lost...
October 31, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29074607/targeting-the-metabolic-axis-acsl-scd-in-colorectal-cancer-progression-by-therapeutic-mirnas-mir-19b-1-role
#9
Silvia Cruz-Gil, Ruth Sanchez-Martinez, Marta Gomez de Cedron, Roberto Martin-Hernandez, Teodoro Vargas, Susana Molina, Jesus Herranz, Alberto Davalos, Guillermo Reglero, Ana Ramirez de Molina
Abnormal acyl-CoA synthetase/ stearoyl-CoA desaturase (ACSL/SCD) lipid network fuels colon cancer progression endowing cells with invasive and migratory properties. Therapies against this metabolic network may be useful to improve clinical outcomes. Since miRNAs (miRNAs/miR) are important epigenetic regulators, we investigated novel miRNAs targeting this pro-tumorigenic axis; and hence to be used both as therapeutic or prognostic miRNAs. Thirty-one putative common miRNAs were predicted to target simultaneously the three enzymes comprising ACSL/SCD network...
October 26, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29066466/dgk%C3%AE-deficiency-protects-against-peripheral-insulin-resistance-and-improves-energy-metabolism
#10
Boubacar Benziane, Melissa L Borg, Robby Z Tom, Isabelle Riedl, Julie Massart, Marie Björnholm, Marc Gilbert, Alexander V Chibalin, Juleen R Zierath
Diacylglycerol kinases (DGK) regulate the balance between diacylglycerol (DAG) and phosphatidic acid. DGKζ is highly abundant in skeletal muscle and induces fiber hypertrophy. We hypothesized DGKζ influences functional and metabolic adaptions in skeletal muscle and whole body fuel utilization. DAG content was increased in skeletal muscle and adipose tissue, but unaltered in liver of DGKζ knockout (KO) mice. Linear growth, body weight, fat mass, and lean mass was reduced in DGKζ KO versus wild-type mice...
October 24, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29046341/influence-of-the-membrane-environment-on-cholesterol-transfer
#11
Jeffrey Michael Breidigan, Natalie Krzyzanowski, Yangmingyue Liu, Lionel Porcar, Ursula Perez-Salas
Cholesterol, an essential component in biological membranes, is highly unevenly distributed within the cell, with most localized in the plasma membrane while only a small fraction is found in the endoplasmic reticulum, where it is synthesized. The mechanism thought to be driving such distribution gradient is the thermodynamic landscape cellular membranes impose on cholesterol, and which modulates transport. Cellular membranes differ in lipid composition and protein content, and these differences can exist across their leaflets too...
October 18, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29042405/sterol-methyltransferase-a-target-for-anti-amoeba-therapy-towards-transition-state-analog-and-suicide-substrate-drug-design
#12
Medhanie E Kidane, Boden H Vanderloop, Wenxu Zhou, Crista D Thomas, Emilio Ramos, Ujjal Singha, Minu Chaudhuri, W David Nes
Ergosterol biosynthesis pathways essential to pathogenic protozoa growth (Haubrich, B. A. et al. 2015. J. Lipid Res. 56: 331-341) and absent from the human host offer new chokepoint targets. Here, we present characterization and cell-based interference of Acanthamoeba spp sterol 24/28methylases (SMT) that catalyze the committed step in C28- and C29-sterol synthesis. Intriguingly, our kinetic analyses suggest 24SMT prefers plant cycloartenol while 28SMT prefers 24(28)methylene lophenol in similar fashion to the substrate preferences of land plant SMT1 and SMT2...
October 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29038122/whales-lifespan-phospholipids-and-cataracts
#13
Douglas Borchman, Raphaela Stimmelmayr, George Craig
This study addresses the question: why do rats get cataracts at two years, dogs at eight years and whales do not develop cataracts for 200 years? Whale lens lipid phase transitions were compared to the phase transitions of other species that were recalculated. The major phospholipids of the whale lens were sphingolipids, mostly dihydrosphingomyelins with an average molar cholesterol/phospholipid ratio of 10. There was a linear correlation between the percentage of lens sphingolipid and lens lipid hydrocarbon chain order until about 60 % sphingolipid...
October 16, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29025869/regulation-of-triacylglycerol-accumulation-and-lipid-droplet-morphology-by-the-novel-thraustochytrid-specific-lipid-droplet-protein-1-tldp1-in-aurantiochytrium-limacinum-f26-b
#14
Takashi Watanabe, Ryo Sakiyama, Yuya Iimi, Satomi Sekine, Eriko Abe, Kazuko H Nomura, Kazuya Nomura, Yohei Ishibashi, Nozomu Okino, Masahiro Hayashi, Makoto Ito
Thraustochytrids are marine single-cell protists that produce large amounts of polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA). They accumulate PUFAs in lipid droplets (LDs), mainly as constituent(s) of triacylglycerol (TG). We identified a novel protein in the LD fraction of Aurantiochytrium limacinum F26-b using 2-dimensional-difference gel electrophoresis (2D-DIGE). The protein clustered with orthologues of thraustochytrids; however, the cluster was evolutionally different from known PAT family proteins or plant LD proteins, and, thus, we named it Thraustochytrid-specific Lipid Droplet Protein 1 (TLDP1)...
October 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29025868/in-situ-visualization-of-glucocerebrosidase-in-human-skin-tissue-zymography-vs-activity-based-probe-labeling
#15
Jeroen van Smeden, Irini M Dijkhoff, Richard W J Helder, Hanin Al-Khakany, Daphne E C Boer, Anne Schreuder, Wouter W Kallemeijn, Samira Absalah, Herman S Overkleeft, Johannes M F G Aerts, Joke A Bouwstra
Epidermal glucocerebrosidase (GBA1), an acid β-glucosidase normally located in lysosomes, converts (glucosyl)ceramides into ceramides, which is crucial to generate an optimal barrier function of the outermost skin layer, the stratum corneum. Here we report on two developed in-situ methods to localize active GBA in human epidermis: i) an optimized zymography method that is less labour intensive and visualizes enzymatic activity with higher resolution than currently reported methods using either substrate 4-methylumbelliferyl-β-D-glucopyranoside or resorufin-β-D-glucopyranoside...
October 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28986437/harmonizing-lipidomics-nist-interlaboratory-comparison-exercise-for-lipidomics-using-standard-reference-material-1950-metabolites-in-frozen-human-plasma
#16
John A Bowden, Alan Heckert, Candice Z Ulmer, Christina M Jones, Jeremy P Koelmel, Laila Abdullah, Linda Ahonen, Yazen Alnouti, Aaron Armando, John M Asara, Takeshi Bamba, John R Barr, Jonas Bergquist, Christoph H Borchers, Joost Brandsma, Susanne B Breitkopf, Tomas Cajka, Amaury Cazenave-Gassiot, Antonio Checa, Michelle A Cinel, Romain A Colas, Serge Cremers, Edward A Dennis, James E Evans, Alexander Fauland, Oliver Fiehn, Michael S Gardner, Timothy J Garrett, Katherine H Gotlinger, Jun Han, Yingying Huang, Aveline Huipeng Neo, Tuulia Hyotylainen, Yoshihiro Izumi, Hongfeng Jiang, Houli Jiang, Jiang Jiang, Maureen Kachman, Reiko Kiyonami, Kristaps Klavins, Christian Klose, Harald C Kofeler, Johan Kolmert, Therese Koal, Grielof Koster, Zsuzsanna Kuklenyik, Irwin J Kurland, Michael Leadley, Karen Lin, Krishna Rao Maddipati, Danielle McDougall, Peter J Meikle, Natalie A Mellett, Cian Monnin, M Arthur Moseley, Renu Nandakumar, Matej Oresic, Rainey E Patterson, David Peake, Jason S Pierce, Martin Post, Anthony D Postle, Rebecca Pugh, Yunping Qui, Oswald Quehenberger, Parsram Ramrup, Jon Rees, Barbara Rembiesa, Denis Reynaud, Mary R Roth, Susanne Sales, Kai Schuhmann, Michal Laniado Schwartzman, Charles N Serhan, Andrej Shevchenko, Stephen E Somerville, Lisa St John-Williams, Michal A Surma, Hiroaki Takeda, Rhishikesh Thakare, J Will Thompson, Federico Torta, Alexander Triebl, Martin Trotzmuller, S J Kumari Ubhayasekera, Dajana Vuckovic, Jacquelyn M Weir, Ruth Welti, Markus R Wenk, Craig E Wheelock, Libin Yao, Min Yuan, Xueqing Heather Zhao, Senlin Zhou
As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950 Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each lab using a different lipidomics workflow. A total of 1527 unique lipids were measured across all laboratories, and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories...
October 6, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28986436/normal-human-adipose-tissue-functions-and-differentiation-in-patients-with-biallelic-lpin1-inactivating-mutations
#17
Michele Pelosi, Eric Testet, Soazig Le Lay, Isabelle Dugail, Xiaoyun Tang, Guillaume Mabilleau, Yamina Hamel, Marine Madrange, Thomas Blanc, Thierry Odent, Todd P W McMullen, Marco Alfò, David N Brindley, Pascale de Lonlay
Lipin-1 is a Mg2+-dependent phosphatidic acid phosphatase (PAP) that in mice is necessary for normal glycerolipid biosynthesis, controlling adipocytes metabolism and adipogenic differentiation. Mice carrying inactivating mutations in the Lpin1 gene display the characteristic features of human familial lipodystrophy. Very little is known on the roles of lipin-1 in human adipocyte physiology. Apparently fat distribution and weight is normal in humans carrying LPIN1 inactivating mutations, but a detailed analysis of adipose tissue appearance and functions in these patients has not been available so far...
October 6, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28912302/prevention-of-renal-apob-retention-is-protective-against-diabetic-nephropathy-role-of-tgf-%C3%AE-inhibition
#18
Patricia G Wilson, Joel C Thompson, Meghan H Yoder, Richard Charnigo, Lisa R Tannock
Animal studies demonstrate that hyperlipidemia and renal lipid accumulation contribute to the pathogenesis of diabetic nephropathy. We previously demonstrated that renal lipoproteins co-localize with biglycan, a renal proteoglycan. The purpose of this study was to determine if prevention of renal lipid (apoB) accumulation attenuates diabetic nephropathy. Biglycan deficient and biglycan wildtype Ldlr-/- mice were made diabetic via streptozotocin and fed a high cholesterol diet. As biglycan deficiency is associated with elevated TGF-b, in some experiments mice were injected with either the TGF-b neutralizing antibody 1D11 or with 13C4, an irrelevant control antibody...
September 14, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28972119/loss-of-fatty-acid-binding-protein-1-alters-the-hepatic-endocannabinoid-system-response-to-a-high-fat-diet
#19
Gregory G Martin, Danilo Landrock, Sarah Chung, Lawrence J Dangott, Avery L McIntosh, John T Mackie, Ann B Kier, Friedhelm Schroeder
Upregulation of the hepatic endocannabinoid (EC) receptor [cannabinoid receptor-1 (CB1)] and arachidonoylethanolamide (AEA) is associated with nonalcoholic fatty liver disease (NAFLD). Male mice fed high-fat diet (HFD) ad libitum also exhibit NAFLD, increased hepatic AEA, and obesity. But, preference for HFD complicates interpretation and almost nothing is known about these effects in females. These issues were addressed by pair-feeding HFD. Similarly to ad libitum-fed HFD, pair-fed HFD also increased WT male and female mouse fat tissue mass (FTM), but preferentially at the expense of lean tissue mass...
November 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28972118/vulnerability-of-dhcr7-mutation-carriers-to-aripiprazole-and-trazodone-exposure
#20
Zeljka Korade, Thiago C Genaro-Mattos, Keri A Tallman, Wei Liu, Krassimira A Garbett, Katalin Koczok, Istvan Balogh, Karoly Mirnics, Ned A Porter
Smith-Lemli-Opitz syndrome is a recessive disorder caused by mutations in 7-dehydrocholesterol reductase (DHCR)7 with a heterozygous (HET) carrier frequency of 1-3%. A defective DHCR7 causes accumulation of 7-dehydrocholesterol (DHC), which is a highly oxidizable and toxic compound. Recent studies suggest that several antipsychotics, including the highly prescribed pharmaceuticals, aripiprazole (ARI) and trazodone (TRZ), increase 7-DHC levels in vitro and in humans. Our investigation was designed to compare the effects of ARI and TRZ on cholesterol (Chol) synthesis in fibroblasts from DHCR7(+/-) human carriers and controls (CTRs)...
November 2017: Journal of Lipid Research
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