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Diacylglycerol lipase

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https://www.readbyqxmd.com/read/28901776/liposomal-delivery-of-diacylglycerol-lipase-beta-inhibitors-to-macrophages-dramatically-enhances-selectivity-and-efficacy-in-vivo
#1
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
#2
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
#3
Yuan Li, Wei-Xing Zong, Wen-Xing Ding
Fatty acids are 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
#4
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
#5
Zhiyang Zhai, Hui Liu, Changcheng Xu, John Shanklin
Photosynthetically-derived sugar provides carbon skeletons for lipid biosynthesis. We have used mutants of Arabidopsis and expression of oleogenic factors to investigate relationships among sugar availability, lipid synthesis and the accumulation of triacylglycerols (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...
August 25, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28801319/pet10p-is-a-yeast-perilipin-that-stabilizes-lipid-droplets-and-promotes-their-assembly
#6
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...
August 11, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28794310/structured-mono-and-diacylglycerols-with-a-high-content-of-medium-chain-fatty-acids
#7
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
https://www.readbyqxmd.com/read/28763157/a-unifying-mathematical-model-of-lipid-droplet-metabolism-reveals-key-molecular-players-in-the-development-of-hepatic-steatosis
#8
Christin Wallstab, Dimitra Eleftheriadou, Theresa Schulz, Georg Damm, Daniel Seehofer, Jürgen Borlak, Hermann-Georg Holzhütter, Nikolaus Berndt
The liver responds to elevated plasma concentrations of free fatty acids (FFAs) with an enhanced uptake of FFAs and their esterification to triacylglycerol (TAG). On the long term this may result in massive hepatic TAG accumulation called steatosis hepatitis. In hepatocytes, the poor water-soluble TAG is packed in specialized organelles: Lipid droplets (LDs) serving as transient cellular deposit and lipoproteins (LPs) transporting TAG and cholesterol esters to extra-hepatic tissues. The dynamics of these organelles is controlled by a variety of regulatory surface proteins (RSPs)...
August 1, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28707153/medium-chain-enriched-diacylglycerol-mce-dag-oil-decreases-body-fat-mass-in-mice-by-increasing-lipolysis-and-thermogenesis-in-adipose-tissue
#9
Haeun Kim, Jee-Hwan Choe, Jong Hun Choi, Hun Jung Kim, Soo Hyun Park, Moon Won Lee, Wooki Kim, Gwang-Woong Go
Medium chain fatty acid (MCFA) escapes the formation of chylomicrons in the small intestine, resulting in energy expenditure through beta-oxidation. Diacylglycerol (DAG) is susceptible to oxidation rather than being stored in the adipose tissue. This study was conducted to verify the effect of MCE-DAG oil on body fat mass in vivo. Male C57BL/6 mice were randomly assigned to four groups (n = 12) as follows: (1) normal diet (18% kcal from fat), (2) canola oil as a control (40% kcal from canola oil), (3) MCE-DAG10 (10% kcal from MCE-DAG + 30% kcal from canola oil), and (4) MCE-DAG20 (20% kcal from MCE-DAG + 20% kcal from canola oil)...
August 2017: Lipids
https://www.readbyqxmd.com/read/28641384/acute-testosterone-deficiency-alters-adipose-tissue-fatty-acid-storage
#10
RANDOMIZED CONTROLLED TRIAL
Sylvia Santosa, Nikki C Bush, Michael D Jensen
Context: Although the long-term effects of testosterone on adipose tissue lipid metabolism in men have been defined, the short-term regulation of these effects is not well understood. Objective: We examined the effects of acute testosterone withdrawal on subcutaneous abdominal and femoral adipose tissue fatty acid (FA) storage and cellular mechanisms. Design: This was a prospective, randomized trial. Setting: Mayo Clinic Clinical Research Unit...
August 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28589628/chemical-tools-to-modulate-2-arachidonoylglycerol-biosynthesis
#11
REVIEW
Hui Deng, Mario van der Stelt
2-Arachidonoylglycerol (2-AG) is an important endogenous signaling lipid that activates the cannabinoid receptors (CB1 R and CB2 R), thereby regulating a diverse range of physiological processes including anxiety, appetite, inflammation, memory, pain sensation, and nociception. Diacylglycerol lipases (DAGLs) are the principle enzymes responsible for 2-AG biosynthesis. Recently, the (patho)physiological functions of DAGLs have been explored by both genetic methods and chemical tools. This review will focus on the recent efforts to develop highly selective and in vivo active DAGLs inhibitors using activity-based protein profiling...
June 6, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28585198/fat-cell-and-fatty-acid-turnover-in-obesity
#12
REVIEW
Atilla Engin
The ratio of free fatty acid (FFA) turnover decreases significantly with the expansion of white adipose tissue. Adipose tissue and dietary saturated fatty acid levels significantly correlate with an increase in fat cell size and number. Inhibition of adipose triglyceride lipase leads to an accumulation of triglyceride, whereas inhibition of hormone-sensitive lipase leads to the accumulation of diacylglycerol. The G0/G1 switch gene 2 increases lipid content in adipocytes and promotes adipocyte hypertrophy through the restriction of triglyceride turnover...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28510703/long-chain-fatty-acid-triglyceride-tg-metabolism-disorder-impairs-male-fertility-a-study-using-adipose-triglyceride-lipase-deficient-mice
#13
Hidetake Masaki, Namhyo Kim, Hitomi Nakamura, Keiichi Kumasawa, Eriko Kamata, Ken-Ichi Hirano, Tadashi Kimura
STUDY QUESTION: Does the deletion of adipose triglyceride lipase (Atgl) gene impair male fertility? SUMMARY ANSWER: The deletion of Atgl gene impaired male fertility but the effect was partially reversed by a low long-chain triglyceride (TG) diet. WHAT IS KNOWN ALREADY: ATGL specifically hydrolyses long-chain fatty acid TG to diacylglycerol and a high level of expression of ATGL in testes has been reported. However, the role of ATGL in male fertility is unknown...
July 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28456765/the-skeletal-and-heart-muscle-triacylglycerol-lipolysis-revisited
#14
M Knapp, J Gorski
For 40 years, the enzyme hormone sensitive lipase was considered to hydrolyze the first ester bond of the triacylglycerol moiety and thus initiate hydrolysis. However, 12 years ago a new lipolytic enzyme, termed adipose triglyceride lipase was discovered. It was further shown that the process of lipolysis of triacylglycerol to diacylglycerol and fatty acid is initiated by adipose triglyceride lipase and not by hormone sensitive lipase, responsible for hydrolysis of diacylglycerol to monoacyglycerol and fatty acid...
February 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28440729/2-arachidonoylglycerol-endocannabinoid-signaling-coupled-to-metabotropic-glutamate-receptor-type-5-modulates-anxiety-like-behavior-in-the-rat-ventromedial-prefrontal-cortex
#15
Ana F Almeida-Santos, Fabricio A Moreira, Francisco S Guimaraes, Daniele C Aguiar
2-Arachidonoylglycerol and anandamide are the main endocannabinoids, which act through cannabinoid type-1 and type-2 receptors. Among its many functions, anandamide modulates anxiety-like behaviors in the ventromedial prefrontal cortex. The role of 2-arachidonoylglycerol in this region, however, has remained unclear. Here, we verified whether intra- ventromedial prefrontal cortex injection of 2-arachidonoylglycerol or URB602, a monoacylglycerol lipase inhibitor (responsible for 2-arachidonoylglycerol hydrolysis), induce anxiolytic-like effects in Wistar rats...
June 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28430962/ulk1-prevents-cardiac-dysfunction-in-obesity-through-autophagy-meditated-regulation-of-lipid-metabolism
#16
Minae An, Dong-Ryeol Ryu, Jang Won Park, Ji Ha Choi, Eun-Mi Park, Kyung Eun Lee, Minna Woo, Minsuk Kim
Aims: Autophagy is essential to maintain tissue homeostasis, particularly in long-lived cells such as cardiomyocytes. Whereas many studies support the importance of autophagy in the mechanisms underlying obesity-related cardiac dysfunction, the role of autophagy in cardiac lipid metabolism remains unclear. In the heart, lipotoxicity is exacerbated by cardiac lipoprotein lipase (LPL), which mediates accumulation of fatty acids to the heart through intravascular triglyceride (TG) hydrolysis...
August 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28420705/synthesis-of-neutral-ether-lipid-monoalkyl-diacylglycerol-by-lipid-acyltransferases
#17
Zhengping Ma, Joelle M Onorato, Luping Chen, David W Nelson, Chi-Liang Eric Yen, Dong Cheng
In mammals, ether lipids exert a wide spectrum of signaling and structural functions, such as stimulation of immune responses, anti-tumor activities, and enhancement of sperm functions. Abnormal accumulation of monoalkyl-diacylglycerol (MADAG) was found in Wolman's disease, a human genetic disorder defined by a deficiency in lysosomal acid lipase. In the current study, we found that among the nine recombinant human lipid acyltransferases examined, acyl-CoA:diacylglycerol acyltransferase (DGAT)1, DGAT2, acyl-CoA:monoacylglycerol acyltransferase (MGAT)2, MGAT3, acyl-CoA:wax-alcohol acyltransferase 2/MFAT, and DGAT candidate 3 were able to use 1-monoalkylglycerol (1-MAkG) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG)...
June 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28377876/cannabinoid-type-1-receptor-containing-axons-innervate-npy-agrp-neurons-in-the-mouse-arcuate-nucleus
#18
Yury M Morozov, Marco Koch, Pasko Rakic, Tamas L Horvath
OBJECTIVES: Phytocannabinoids, such as THC and endocannabinoids, are well known to promote feeding behavior and to control energy metabolism through cannabinoid type 1 receptors (CB1R). However, the underlying mechanisms are not fully understood. Generally, cannabinoid-conducted retrograde dis-inhibition of hunger-promoting neurons has been suggested to promote food intake, but so far it has not been demonstrated due to technical limitations. METHODS: We applied immunohistochemical labeling of CB1R for light microscopy and electron microscopy combined with three-dimensional reconstruction from serial sections in CB1R-expressing and CB1R-null mice, which served as a negative control...
April 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28356298/activation-of-cb1-receptors-by-2-arachidonoylglycerol-attenuates-vasoconstriction-induced-by-u46619-and-angiotensin-ii-in-human-and-rat-pulmonary-arteries
#19
Olga Karpińska, Marta Baranowska-Kuczko, Monika Kloza, Ewa Ambroz Ewicz, Tomasz Kozłowski, Irena Kasacka, Barbara Malinowska, Hanna Kozłowska
Recent evidence suggests that endocannabinoids acting via cannabinoid CB1 receptors may modulate vascular responses of various vasoconstrictors in the rodent systemic vasculature. The aim of the study was to investigate whether endocannabinoids modulate the contractile responses evoked by a thromboxane A2 analog (U46619), angiotensin II (ANG II), serotonin (5-HT), and phenylephrine, which stimulate distinct Gq/11 protein-coupled receptors (thromboxane, ANG II type 1, 5-HT2, and α1-adrenergic receptors) in isolated endothelium-intact human and rat pulmonary arteries (hPAs and rPAs, respectively)...
June 1, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28315677/rimonabant-a-selective-cannabinoid1-receptor-antagonist-protects-against-light-induced-retinal-degeneration-in-vitro-and-in-vivo
#20
Tomoyo Imamura, Kazuhiro Tsuruma, Yuki Inoue, Tomohiro Otsuka, Yuta Ohno, Shiho Ogami, Shinsaku Yamane, Masamitsu Shimazawa, Hideaki Hara
The endocannabinoid system is involved in some neurodegenerative diseases such as Alzheimer's disease. An endogenous constellation of proteins related to cannabinoid1 receptor signaling, including free fatty acids, diacylglycerol lipase, and N-acylethanolamine-hydrolyzing acid amidase, are localized in the murine retina. Moreover, the expression levels of endogenous agonists of cannabinoid receptors are changed in the vitreous fluid. However, the role of the endocannabinoid system in the retina, particularly in the light-induced photoreceptor degeneration, remains unknown...
May 15, 2017: European Journal of Pharmacology
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