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Diacylglycerol lipase

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https://www.readbyqxmd.com/read/29151076/modulation-of-the-endocannabinoid-system-by-the-fatty-acid-amide-hydrolase-monoacylglycerol-and-diacylglycerol-lipase-inhibitors-as-an-attractive-target-for-secretory-diarrhoea-therapy
#1
A Wasilewski, A Misicka, M Sacharczuk, J Fichna
Secretory diarrhoea is a leading cause of mortality and morbidity worldwide. Our aim was to characterize the effect of inhibition of selected enzymes involved in the synthesis or degradation of endocannabinoids on electrolyte equilibrium in the mouse colonic tissue. The aim of this study was to evaluate the effects of PF-3845, JZL-184 and RHC-80267, as inhibitors of fatty acid amide hydrolase (FAAH), monoacylglycerol (MAGL) and diacylglycerol lipase (DAGL), respectively on epithelial ion transport in isolated mouse colon stimulated by forskolin (FSK), veratridine (VER) and bethanechol (BET)...
August 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29145497/rare-genetic-variants-in-the-endocannabinoid-system-genes-cnr1-and-dagla-are-associated-with-neurological-phenotypes-in-humans
#2
Douglas R Smith, Christine M Stanley, Theodore Foss, Richard G Boles, Kevin McKernan
Rare genetic variants in the core endocannabinoid system genes CNR1, CNR2, DAGLA, MGLL and FAAH were identified in molecular testing data from 6,032 patients with a broad spectrum of neurological disorders. The variants were evaluated for association with phenotypes similar to those observed in the orthologous gene knockouts in mice. Heterozygous rare coding variants in CNR1, which encodes the type 1 cannabinoid receptor (CB1), were found to be significantly associated with pain sensitivity (especially migraine), sleep and memory disorders-alone or in combination with anxiety-compared to a set of controls without such CNR1 variants...
2017: PloS One
https://www.readbyqxmd.com/read/29138223/effect-of-maternal-high-fat-diet-on-key-components-of-the-placental-and-hepatic-endocannabinoid-system
#3
Kushal Gandhi, Cun Li, Nadezhda German, Cezary Skobowiat, Maira Carrillo, Raja Reddy Kallem, Eneko Larumbe, Stacy Martinez, Marcel Chuecos, Gary Ventolini, Peter Nathanielsz, Natalia Schlabritz-Loutsevitch
INTRODUCTION: Involvement of endogenous cannabinoids (eCBs) in obesity is well-characterized. However, information regarding eCB physiology in obesity associated with pregnancy is sparse. METHODS: From at least 9 months before conception, non-pregnant baboons (Papio spp.) were fed a diet of either 45% fat (HFD; n=11) or 12% fat or a control diet (CTR; n=11), and dietary intervention continued through pregnancy. Maternal and fetal venous plasma samples were evaluated using liquid chromatography-mass spectrometry to quantify anandamide (AEA) and 2-arachidonoyl glycerol (2-AG)...
November 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29109080/central-leptin-regulates-heart-lipid-content-by-selectively-increasing-ppar-%C3%AE-%C3%AE-expression
#4
Cristina Mora, Cristina Pintado, Blanca Rubio, Lorena Mazuecos, Virginia Lopez, Alejandro Fernandez, Aurora Salamanca, Brenda Barcena, Teresa Fernandez-Agullo, Carmen Arribas, Nilda Gallardo, Antonio Andres
The role of central leptin in regulating the heart from lipid accumulation in lean leptin-sensitive animals has not been fully elucidated. Herein we investigated the effects of central leptin infusion on the expression of genes involved in cardiac metabolism and its role in the control of myocardial triacylglyceride (TAG) accumulation in adult Wistar rats. Intracerebroventricular (icv) leptin infusion (0.2µg/day) for 7 days markedly decreased TAG levels in cardiac tissue. Remarkably, the cardiac anti-steatotic effects of central leptin were associated with the selective up-regulation of gene and protein expression of peroxisome proliferator-activated receptor β/δ (PPARβ/δ) and their target genes, adipose triglyceride lipase (ATGL), hormone sensitive lipase (HSL), pyruvate dehydrogenase kinase 4 (PDK4), and acyl CoA oxidase 1 (Acox1), involved in myocardial intracellular lipolysis and mitochondrial/peroxisomal fatty acid utilization...
November 6, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/29102548/modulation-of-the-glycerol-phosphate-availability-led-to-concomitant-reduction-in-the-citric-acid-excretion-and-increase-in-lipid-content-and-yield-in-yarrowia-lipolytica
#5
Rana Sagnak, Sandrine Cochot, Carole Molina-Jouve, Jean-Marc Nicaud, Stéphane E Guillouet
In order to improve TriAcylGycerol (TAG) lipids accumulation in the yeast Yarrowia lipolytica on glucose, double over-expression of the major acyl-CoA:diacylglycerol acyltransferase encoding gene (ylDGA2) and of the glycerol-phosphate dehydrogenase encoding gene (ylGPD1) was carried out. The genes were over-expressed in a strain impaired for the mobilization of the accumulated lipids, through the deletion of the genes encoding acyl-coenzyme A oxidases (POX1-6 genes) and the deletion of the very efficient lipase attached to the lipid bodies, encoded by ylTGL4...
November 2, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/29100630/stress-promotes-drug-seeking-through-glucocorticoid-dependent-endocannabinoid-mobilization-in-the-prelimbic-cortex
#6
Jayme R McReynolds, Elizabeth M Doncheck, Yan Li, Oliver Vranjkovic, Evan N Graf, Daisuke Ogasawara, Benjamin F Cravatt, David A Baker, Qing-Song Liu, Cecilia J Hillard, John R Mantsch
BACKGROUND: Clinical reports suggest that rather than directly driving cocaine use, stress may create a biological context within which other triggers for drug use become more potent. We hypothesize that stress-induced increases in corticosterone "set the stage" for relapse by promoting endocannabinoid-induced attenuation of inhibitory transmission in the prelimbic cortex (PL). METHODS: We have established a rat model for these stage-setting effects of stress. In this model, neither a stressor (electric footshock) nor stress-level corticosterone treatment alone reinstates cocaine seeking following self-administration and extinction, but each treatment potentiates reinstatement in response to an otherwise subthreshold cocaine priming dose (2...
October 6, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29082418/effects-of-organic-solvent-water-activity-and-salt-hydrate-pair-on-the-sn-1-3-selectivity-and-activity-of-whole-cell-lipase-from-aspergillus-niger-gzuf36
#7
Cuiqin Li, Fuhao Zhang, Zexin Gao, Laping He, Xuefeng Zeng, Qiujin Zhu, Lijuan Yu
We previously screened a whole-cell lipase EC 3.1.1.3 from the novel strain Aspergillus niger GZUF36, which exhibited 1,3-selectivity in the synthesis of 1,3-diacylglycerol via glycerolysis. However, the mechanism of lipase selectively in catalyzing the sn-1,3 position remains ambiguous. This work was performed to investigate the 1,3-selective mechanism of lipase using glycerolysis to synthesize 1,3-diacylglycerol (1,3-DG) as a model reaction by changing solvent(s) and water activity (aw), and addition of salt hydrate pair...
October 29, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29031792/control-of-myogenic-tone-and-agonist-induced-contraction-of-intramural-coronary-resistance-arterioles-by-cannabinoid-type-1-receptors-and-endocannabinoids
#8
Mária Szekeres, György L Nádasy, Eszter Soltész-Katona, László Hunyady
It was tested whether intrinsic CB1R activation modifies myogenic and agonist induced contraction of intramural coronary resistance arteries of the rat. CB1R protein was detected by immuno-histochemistry and by Western blot, its mRNA by qRT-PCR in their wall. Microsurgically prepared cylindrical coronary segments (∼100-150μm) developed myogenic contraction (∼20% of relaxed luminal diameter), from which a substantial relaxation (∼15%) in response to WIN55212 (a specific agonist of the CB1Rs) has been found...
October 16, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28980889/comparative-analysis-of-effects-of-dietary-arachidonic-acid-and-epa-on-growth-tissue-fatty-acid-composition-antioxidant-response-and-lipid-metabolism-in-juvenile-grass-carp-ctenopharyngodon-idellus
#9
COMPARATIVE STUDY
Jing-Jing Tian, Cai-Xia Lei, Hong Ji, Gen Kaneko, Ji-Shu Zhou, Hai-Bo Yu, Yang Li, Er-Meng Yu, Jun Xie
Four isonitrogenous and isoenergetic purified diets containing free arachidonic acid (ARA) or EPA (control group), 0·30 % ARA, 0·30 % EPA and 0·30 % ARA+EPA (equivalent) were designed to feed juvenile grass carp (10·21 (sd 0·10) g) for 10 weeks. Only the EPA group presented better growth performance compared with the control group (P<0·05). Dietary ARA and EPA were incorporated into polar lipids more than non-polar lipids in hepatopancreas but not intraperitoneal fat (IPF) tissue. Fish fed ARA and EPA showed an increase of serum superoxide dismutase and catalase activities, and decrease of glutathione peroxidase activity and malondialdehyde contents (P<0·05)...
September 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28980208/calcitriol-concomitantly-enhances-insulin-sensitivity-and-alters-myocellular-lipid-partitioning-in-high-fat-treated-skeletal-muscle-cells
#10
Grace E Jefferson, David M Schnell, D Travis Thomas, Lance M Bollinger
Vitamin D reduces myocellular insulin resistance, but the effects of vitamin D on intramyocellular lipid (IMCL) partitioning are unknown. The purpose of this study was to understand how calcitriol, the active vitamin D metabolite, affects insulin sensitivity and lipid partitioning in skeletal muscle cells. C2C12 myotubes were treated with calcitriol (100 nM) or vehicle control for 96 h. Insulin-stimulated Akt phosphorylation (Thr 308) was determined by western blot. Intramyocellular triacylglycerol (IMTG), diacylglycerol (DAG), and ceramide content were measured by LC/MS...
November 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28970359/investigation-of-diacylglycerol-lipase-alpha-inhibition-in-the-mouse-lipopolysaccharide-inflammatory-pain-model
#11
Jenny L Wilkerson, Giulia Donvito, Travis W Grim, Rehab A Abdullah, Daisuke Ogasawara, Benjamin F Cravatt, Aron H Lichtman
Diacylglycerol lipase (DAGL) α and β, the major biosynthetic enzymes of the endogenous cannabinoid (endocannabinoid) 2-arachidonylglycerol (2-AG), are highly expressed in the nervous system and immune system, respectively. Genetic deletion or pharmacological inhibition of DAGL-β protects against lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages, and reverses LPS-induced allodynia in mice. In order to gain insight into the contribution of DAGL-α in LPS-induced allodynia, we tested global knockout mice as well as DO34, a dual DAGL-α/-β inhibitor...
October 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28948493/highly-efficient-deacidification-of-high-acid-rice-bran-oil-using-methanol-as-a-novel-acyl-acceptor
#12
Daoming Li, Muniba Faiza, Shahid Ali, Weifei Wang, Chin Ping Tan, Bo Yang, Yonghua Wang
A highly efficient process for reducing the fatty acid (FA) content of high-acid rice bran oil (RBO) was developed by immobilized partial glycerides-selective lipase SMG1-F278N-catalyzed esterification/transesterification using methanol as a novel acyl acceptor. Molecular docking simulation indicated that methanol was much closer to the catalytic serine (Ser-171) compared with ethanol and glycerol, which might be one of the reasons for its high efficiency in the deacidification of high-acid RBO. Additionally, the reaction parameters were optimized to minimize the FA content of high-acid RBO...
September 25, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28946274/a-lumped-model-of-the-lipase-catalyzed-hydrolysis-of-sardine-oil-to-maximize-polyunsaturated-fatty-acids-content-in-acylglycerols
#13
R Morales-Medina, M Munio, A Guadix, E M Guadix, F Camacho
The aim of this work was to produce diacylglycerols (DAG) and monoacylglycerols (MAG) with a high content of polyunsaturated fatty acids (PUFA). Rhizomucor miehei lipase mediated-hydrolysis of sardine oil was conducted at several water activities. The system was mechanistically modeled to predict the time evolution of the concentration of triacylglycerols, DAG, MAG and free fatty acids (FFA) and the concentration of saturated, mono- and polyunsaturated fatty acids. The release of the first fatty acid from the triacylglycerol was independent on the unsaturation degree...
February 1, 2018: Food Chemistry
https://www.readbyqxmd.com/read/28901776/liposomal-delivery-of-diacylglycerol-lipase-beta-inhibitors-to-macrophages-dramatically-enhances-selectivity-and-efficacy-in-vivo
#14
Myungsun Shin, Helena W Snyder, Giulia Donvito, Lesley D Schurman, Todd E Fox, Aron H Lichtman, Mark Kester, Ku-Lung Hsu
Diacylglycerol lipase-beta (DAGLβ) hydrolyzes arachidonic acid (AA)-containing diacylglycerols to produce bioactive lipids including endocannabinoids and AA-derived eicosanoids involved in regulation of inflammatory signaling. Previously, we demonstrated that DAGLβ inactivation using the triazole urea inhibitor KT109 blocked macrophage inflammatory signaling and reversed allodynic responses of mice in inflammatory and neuropathic pain models. Here, we tested whether we could exploit the phagocytic capacity of macrophages to localize delivery of DAGLβ inhibitors to these cells in vivo using liposome encapsulated KT109...
September 13, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28873723/substrates-emulsification-process-to-improve-lipase-catalyzed-sardine-oil-glycerolysis-in-different-systems-evaluation-of-lipid-oxidation-of-the-reaction-products
#15
Ángela García Solaesa, María Teresa Sanz, Rodrigo Melgosa, Sagrario Beltrán
Mono- and diacylglycerols rich in omega-3 have a great interest due to their good bioavailability and oxidation stability compared with other kind of omega-3 concentrates. The main drawback in mono- and diacylglycerols production by glycerolysis is the immiscibility of the substrates, oil and glycerol. To improve mass transfer rates, avoiding the use of organic solvents, emulsification of both reactants as reverse micelles (glycerol-in-oil) was carried out previous to lipase-catalyzed sardine oil glycerolysis...
October 2017: Food Research International
https://www.readbyqxmd.com/read/28873005/recycling-the-danger-via-lipid-droplet-biogenesis-after-autophagy
#16
Yuan Li, Wei-Xing Zong, Wen-Xing Ding
Fatty acids are an important cellular energy source under starvation conditions. However, excessive free fatty acids (FFAs) in the cytoplasm cause lipotoxicity. Therefore, it is important to understand the mechanisms by which cells mobilize lipids and maintain a homeostatic level of fatty acids. Recent evidence suggests that cells can break down lipid droplets (LDs), the intracellular organelles that store neutral lipids, via PNPLA2/adipose triglyceride lipase and a selective type of macroautophagy/autophagy termed lipophagy, to release FFAs under starvation conditions...
September 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28844762/2-arachidonoylglycerol-metabolism-is-differently-modulated-by-oligomeric-and-fibrillar-conformations-of-amyloid-beta-in-synaptic-terminals
#17
Ana C Pascual, Virginia L Gaveglio, Norma M Giusto, Susana J Pasquaré
Alzheimer's disease (AD) is the most prevalent disorder of senile dementia mainly characterized by amyloid-beta peptide (Aβ) deposits in the brain. Cannabinoids are relevant to AD as they exert several beneficial effects in many models of this disease. Still, whether the endocannabinoid system is either up- or down-regulated in AD has not yet been fully elucidated. Thus, the aim of the present paper was to analyze endocannabinoid 2-arachidonoylglycerol (2-AG) metabolism in cerebral cortex synaptosomes incubated with Aβ oligomers or fibrils...
August 24, 2017: Neuroscience
https://www.readbyqxmd.com/read/28842550/sugar-potentiation-of-fatty-acid-and-triacylglycerol-accumulation
#18
Zhiyang Zhai, Hui Liu, Changcheng Xu, John Shanklin
Photosynthetically derived sugar provides carbon skeletons for lipid biosynthesis. We used mutants of Arabidopsis (Arabidopsis thaliana) and the expression of oleogenic factors to investigate relationships among sugar availability, lipid synthesis, and the accumulation of triacylglycerol (TAG) in leaf tissue. The adg1 mutation disables the small subunit of ADP-glucose pyrophosphorylase, the first step in starch synthesis, and the suc2 mutation disables a sucrose/proton symporter that facilitates sucrose loading from leaves into phloem...
October 2017: Plant Physiology
https://www.readbyqxmd.com/read/28801319/pet10p-is-a-yeast-perilipin-that-stabilizes-lipid-droplets-and-promotes-their-assembly
#19
Qiang Gao, Derk D Binns, Lisa N Kinch, Nick V Grishin, Natalie Ortiz, Xiao Chen, Joel M Goodman
Pet10p is a yeast lipid droplet protein of unknown function. We show that it binds specifically to and is stabilized by droplets containing triacylglycerol (TG). Droplets isolated from cells with a PET10 deletion strongly aggregate, appear fragile, and fuse in vivo when cells are cultured in oleic acid. Pet10p binds early to nascent droplets, and their rate of appearance is decreased in pet10Δ Moreover, Pet10p functionally interacts with the endoplasmic reticulum droplet assembly factors seipin and Fit2 to maintain proper droplet morphology...
October 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28794310/structured-mono-and-diacylglycerols-with-a-high-content-of-medium-chain-fatty-acids
#20
Alaina A Esperón-Rojas, R Baeza-Jiménez, Cynthia Cano-Sarmiento, Hugo S García
In the present work, direct enzyme-catalysed esterification of medium chain fatty acids (MCFA) from three different sources (Medium chain triacylglycerols, MCT; saponified MCT and a mixture of free MCFA) was evaluated to obtain structured mono- and diacylglycerols. The esterifications were carried out mixing the different sources of MCFA with glycerol at two weight ratios (1:1 and 4:1, w/w), using three immobilized lipases: Novozym 435, Lipozyme RM IM and Lipozyme TL IM; different reaction times (t = 0, 15, 30, 60, 120 min); enzyme loadings (5, 10 or 15% with respect to the total weight of substrates)...
August 8, 2017: Journal of Oleo Science
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