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https://www.readbyqxmd.com/read/29331500/peripheral-modulation-of-the-endocannabinoid-system-in-metabolic-disease
#1
REVIEW
Nirajan Shrestha, James S M Cuffe, Dana S Hutchinson, John P Headrick, Anthony V Perkins, Andrew J McAinch, Deanne H Hryciw
Dysfunction of the endocannabinoid system (ECS) has been identified in metabolic disease. Cannabinoid receptor 1 (CB1) is abundantly expressed in the brain but also expressed in the periphery. Cannabinoid receptor 2 (CB2) is more abundant in the periphery, including the immune cells. In obesity, global antagonism of overexpressed CB1 reduces bodyweight but leads to centrally mediated adverse psychological outcomes. Emerging research in isolated cultured cells or tissues has demonstrated that targeting the endocannabinoid system in the periphery alleviates the pathologies associated with metabolic disease...
January 10, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29330355/fatty-acids-and-related-lipid-mediators-in-the-regulation-of-cutaneous-inflammation
#2
REVIEW
Magdalena Kiezel-Tsugunova, Alexandra C Kendall, Anna Nicolaou
Human skin has a distinct profile of fatty acids and related bioactive lipid mediators that regulate many aspects of epidermal and dermal homeostasis, including immune and inflammatory reactions. Sebum lipids act as effective antimicrobial agents, shape immune cell communications and contribute to the epidermal lipidome. The essential fatty acid linoleic acid is crucial for the structure of the epidermal barrier, while polyunsaturated fatty acids act as precursors to eicosanoids, octadecanoids and docosanoids through cyclooxygenase, lipoxygenase and cytochrome P450 monooxygenase-mediated reactions, and endocannabinoids and N-acyl ethanolamines...
January 12, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29329795/omega-3-fatty-acids-and-adipose-tissue-biology
#3
REVIEW
Ondrej Kuda, Martin Rossmeisl, Jan Kopecky
This review provides evidence for the importance of white and brown adipose tissue (i.e. WAT and BAT) function for the maintenance of healthy metabolic phenotype and its preservation in response to omega-3 polyunsaturated fatty acids (omega-3 PUFA), namely in the context of diseased states linked to aberrant accumulation of body fat, systemic low-grade inflammation, dyslipidemia and insulin resistance. More specifically, the review deals with (i) the concept of immunometabolism, i.e. how adipose-resident immune cells and adipocytes affect each other and define the immune-metabolic interface; and (ii) the characteristic features of "healthy adipocytes" in WAT, which are relatively small fat cells endowed with a high capacity for mitochondrial oxidative phosphorylation, triacylglycerol/fatty acid (TAG/FA) cycling and de novo lipogenesis (DNL)...
January 9, 2018: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29329391/oxidative-burst-and-dectin-1-triggered-phagocytosis-affected-by-norepinephrine-and-endocannabinoids-implications-for-fungal-clearance-under-stress
#4
Judith-Irina Buchheim, Spencer Hoskyns, Dominique Moser, Bing Han, Elisabeth Deindl, Marion Hörl, Katharina Biere, Matthias Feuerecker, Gustav Schelling, Alexander Chouker
A prolonged stress burden is known to hamper the efficiency of both the innate and adaptive immune systems and to attenuate the stress responses by the catecholaminergic and endocannabinoid (EC) systems. Key mechanisms of innate immunity are the eradication of pathogens through phagocytosis and the respiratory burst. We tested the concentration-dependent, spontaneous and stimulated (via TNFα and fMLP) release of reactive oxygen species (ROS) by human PMNs in vitro in response to norepinephrine (NE) and AM1241, a pharmacological ligand for the endocannabinoid receptor CB2...
January 10, 2018: International Immunology
https://www.readbyqxmd.com/read/29329382/adolescent-synthetic-cannabinoid-exposure-produces-enduring-changes-in-dopamine-neuron-activity-in-a-rodent-model-of-schizophrenia-susceptibility
#5
David D Aguilar, Andrea Giuffrida, Daniel J Lodge
Background: Epidemiological studies recognize cannabis intake as a risk factor for schizophrenia, yet the majority of adolescents who use marijuana do not develop psychosis. Similarly, the abuse of synthetic cannabinoids poses a risk for psychosis. For these reasons, it is imperative to understand the effects of adolescent cannabinoid exposure in susceptible individuals. Method: We have recently developed a novel rodent model of schizophrenia susceptibility, the F2 MAM rat, where only a proportion (~40%) of rats display a schizophrenia-like phenotype...
January 10, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29326169/dual-cyclooxygenase-fatty-acid-amide-hydrolase-inhibitor-exploits-novel-binding-interactions-in-the-cyclooxygenase-active-site
#6
Michael C Goodman, Shu Xu, Carol A Rouzer, Surajit Banerjee, Kebreab Ghebreselasie, Marco Migliore, Daniele Piomelli, Lawrence J Marnett
The cyclooxygenases COX-1 and COX-2 oxygenate arachidonic acid (AA) to prostaglandin H2 (PGH2). COX-2 also oxygenates the endocannabinoids, 2-arachidonoylglycerol (2-AG) and arachidonoylethanolamide (AEA), to the corresponding PGH2 analogs. Both enzymes are targets of nonsteroidal anti-inflammatory drugs (NSAIDs), but NSAID-mediated COX inhibition is associated with gastrointestinal toxicity. One potential strategy to counter this toxicity is to also inhibit fatty acid amide hydrolase (FAAH), which hydrolyzes bioactive fatty acid ethanolamides (FAEs) into fatty acids and ethanolamine...
January 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29325757/the-role-of-fatty-acids-and-their-endocannabinoid-like-derivatives-in-the-molecular-regulation-of-appetite
#7
REVIEW
Renger F Witkamp
Intake, absorption and synthesis of fatty acids, including those produced by the intestinal microbiota are tightly monitored via specific receptors and, indirectly through their conversion into a variety of signalling molecules. The resulting information is integrated and translated to different physiological processes, including the regulation of appetite and satiation. Direct chemosensing of fatty acids takes place via interaction with free fatty acid (FFA) and other receptors. These are present in the oronasal cavity and along the entire gastrointestinal tract, in various other tissues, and, for some receptors also in brain...
January 8, 2018: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29321244/silencing-carboxylesterase-1-in-human-thp-1-macrophages-perturbs-genes-regulated-by-pparg-rxr-and-rar-rxr-downregulation-of-cyp27a1-lxr%C3%AE-signaling
#8
Lee C Mangum, Xiang Hou, Abdolsamad Borazjani, Jung Hwa Lee, Matthew K Ross, J Allen Crow
Macrophage foam cells store excess cholesterol as cholesteryl esters, which need to be hydrolyzed for cholesterol efflux. We recently reported that silencing expression of carboxylesterase 1 (CES1) in human THP-1 macrophages (CES1KD macrophages) reduced cholesterol uptake and decreased expression of CD36 and scavenger receptor-A in cells loaded with acetylated low-density lipoprotein (acLDL). Here, we report that CES1KD macrophages exhibit reduced transcription of cytochrome P450 27A1 ( CYP27A1 ) in non-loaded and acLDL-loaded cells...
January 10, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29314831/a-fluorescent-probe-to-unravel-functional-features-of-cannabinoid-receptor-cb1-in-human-blood-and-tonsil-immune-system-cells
#9
Mar Martín-Fontecha, Alba Angelina, Beate Rückert, Ainoa Rueda-Zubiaurre, Leticia Martin-Cruz, Willem van de Veen, Mübeccel Akdis, Silvia Ortega-Gutierrez, María L López-Rodrí Guez, Cezmi Akdis, Oscar Palomares
The human endogenous cannabinoid system (ECS) regulates key physiological processes and alterations in its signalling pathways and endocannabinoid levels are associated to diseases such as neurological and neuropsychiatric conditions, cancer, pain and inflammation, obesity, metabolic and different immune related disorders. Immune system cells express the G-protein coupled cannabinoid receptor 1 (CB1) but its functional role has not been fully understood, likely due to the lack of appropriate tools. The availability of novel tools to investigate the role of CB1 in immune regulation might contribute to identify CB1 as a potential novel therapeutic target or biomarker for many diseases...
January 9, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29313885/interferon-%C3%AE-treatment-increases-endocannabinoid-and-related-n-acylethanolamine-levels-in-t84-human-colon-carcinoma-cells
#10
Mireille Alhouayek, Linda Rankin, Sandra Gouveia-Figueira, Christopher J Fowler
BACKGROUND AND PURPOSE: Endocannabinoids and related N-acylethanolamines (NAEs) are involved in regulation of gut function, but relatively little is known as to whether inflammatory cytokines such as interferon γ (IFNγ) affect their levels. We have investigated this in vitro using T84 colon cancer cells, which when cultured in monolayers differentiate to form adult colonic crypt-like cells with excellent permeability barrier properties. EXPERIMENTAL APPROACH: NAE levels were determined by ultra-performance liquid chromatography-tandem mass spectrometric analysis...
January 3, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29313138/do-psychoactive-drugs-have-a-therapeutic-role-in-compulsivity-studies-on-schedule-induced-polydipsia
#11
Elena Martín-González, Ángeles Prados-Pardo, Santiago Mora, Pilar Flores, Margarita Moreno
RATIONALE: Clinical studies have shown that some psychoactive recreational drugs have therapeutic applications in anxiety, depression, and schizophrenia. However, to date, there are few studies on the therapeutic potential efficacy of recreational drugs in compulsive neuropsychiatric disorders. OBJECTIVES: We explored the therapeutic potential of different psychoactive and psychedelic drugs in a preclinical model of compulsive behavior. METHODS: Outbred male Wistar rats were selected as either high (HD) or low (LD) drinkers according to their behavior in schedule-induced polydipsia (SIP)...
January 8, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29310960/cannabinoid-hyperemesis-syndrome-pathophysiology-and-treatment-in-the-emergency-department
#12
John R Richards
BACKGROUND: Cannabinoid hyperemesis syndrome (CHS) is a challenging clinical disorder. CHS patients frequently present to the emergency department and may require treatment for intractable emesis, dehydration, and electrolyte abnormalities. Thought to be a variant of cyclic vomiting syndrome, CHS has become more prevalent with increasing cannabis potency and use, as enabled by various states having legalized the recreational use of cannabis. OBJECTIVE: This aim of this review is to investigate the pathophysiology of CHS and evaluate the published literature on pharmacologic treatment in the emergency department...
January 5, 2018: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/29310667/wwl70-protects-against-chronic-constriction-injury-induced-neuropathic-pain-in-mice-by-cannabinoid-receptor-independent-mechanisms
#13
Jie Wen, Melissa Jones, Mikiei Tanaka, Prabhuanand Selvaraj, Aviva J Symes, Brian Cox, Yumin Zhang
BACKGROUND: Targeting the endocannabinoid system has emerged as an effective strategy for the treatment of inflammatory and neurological diseases. Unlike the inhibition of the principal 2-arachidonyl glycerol (2-AG) hydrolytic enzyme monoacylglycerol lipase (MAGL), which leads to 2-AG overload and cannabinoid receptor desensitization, selective inhibition of the minor 2-AG hydrolytic enzyme alpha, beta-hydrolase domain 6 (ABHD6) can provide therapeutic benefits without producing cannabimimetic side effects...
January 8, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29310193/re-the-endocannabinoid-system-a-target-for-the-treatment-of-luts
#14
Alan J Wein
No abstract text is available yet for this article.
January 2018: Journal of Urology
https://www.readbyqxmd.com/read/29309142/discovery-of-1-5-diphenylpyrazole-3-carboxamide-derivatives-as-potent-reversible-and-selective-monoacylglycerol-lipase-magl-inhibitors
#15
Mojgan Aghazadeh Tabrizi, Pier Giovanni Baraldi, Stefania Baraldi, Emanuela Ruggiero, Lucia De Stefano, Flavio Rizzolio, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Andrea Chicca, Margherita Lapillo, Jürg Gertsch, Clementina Manera, Marco Macchia, Adriano Martinelli, Carlotta Granchi, Filippo Minutolo, Tiziano Tuccinardi
Monoacylglycerol lipase (MAGL) is a serine hydrolase that plays an important role in the degradation of the endocannabinoid neurotransmitter 2-arachidonoylglycerol, which is implicated in many physiological processes. Beyond the possible utilization of MAGL inhibitors as anti-inflammatory, anti-nociceptive and anti-cancer agents, their application has encountered obstacles due to the unwanted effects caused by the irreversible inhibition of this enzyme. The possible application of reversible MAGL inhibitors has only recently been explored, mainly due to the deficiency of known compounds possessing efficient reversible inhibitory activities...
January 8, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29304078/the-endocannabinoid-gene-faah2a-modulates-stress-associated-behavior-in-zebrafish
#16
Randall G Krug, Han B Lee, Louis Y El Khoury, Ashley N Sigafoos, Morgan O Petersen, Karl J Clark
The ability to orchestrate appropriate physiological and behavioral responses to stress is important for survival, and is often dysfunctional in neuropsychiatric disorders that account for leading causes of global disability burden. Numerous studies have shown that the endocannabinoid neurotransmitter system is able to regulate stress responses and could serve as a therapeutic target for the management of these disorders. We used quantitative reverse transcriptase-polymerase chain reactions to show that genes encoding enzymes that synthesize (abhd4, gde1, napepld), enzymes that degrade (faah, faah2a, faah2b), and receptors that bind (cnr1, cnr2, gpr55-like) endocannabinoids are expressed in zebrafish (Danio rerio)...
2018: PloS One
https://www.readbyqxmd.com/read/29300902/peripheral-endocannabinoids-associated-with-energy-expenditure-in-native-americans-of-southwestern-heritage
#17
Sascha Heinitz, Alessio Basolo, Paolo Piaggi, Daniele Piomelli, Reiner Jumpertz von Schwartzenberg, Jonathan Krakoff
Context: The endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and the related acylethanolamide oleoylethanolamide (OEA) have been implicated in energy expenditure (EE)-regulation and metabolic diseases. Muscle (fat-free mass, FFM) and fat (fat mass, FM) are metabolically active compartments and main determinants of EE. Objective: To assess whether human muscle, adipose, and plasma endocannabinoids correlate with EE. Design: Muscle, adipose, and plasma AEA, 2-AG, and OEA concentrations were measured via liquid chromatography-mass spectrometry...
December 28, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29288688/neuroprotective-activity-of-macamides-on-manganese-induced-mitochondrial-disruption-in-u-87-mg-glioblastoma-cells
#18
Kuljeet S Gugnani, Nguyen Vu, Alejandro N Rondón-Ortiz, Mark Böhlke, Timothy J Maher, Alejandro J Pino-Figueroa
Macamides are a distinct class of secondary metabolites, benzylamides of long chain fatty acids, which were isolated from the Peruvian plant Lepidium meyenii (Maca). As structural analogues of the endocannabinoid anandamide (AEA), they have demonstrated neuroprotective effects in vitro and in vivo. The purpose of this study was to demonstrate the neuroprotective activity of the macamides: N-(3-methoxybenzyl)oleamide (MAC 18:1), N-(3-methoxybenzyl)linoleamide (MAC 18:2) and N-(3-methoxybenzyl)linolenamide (MAC 18:3) in a neurotoxic environment caused by exposure of U-87 MG glioblastoma cells to manganese chloride (MnCl2)...
December 27, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29285308/decisive-role-of-p42-44-mitogen-activated-protein-kinase-in-%C3%AE-9-tetrahydrocannabinol-induced-migration-of-human-mesenchymal-stem-cells
#19
Ellen Lüder, Robert Ramer, Kirsten Peters, Burkhard Hinz
In past years, medical interest in Δ9-tetrahydrocannabinol (THC), the major psychoactive ingredient of the Cannabis plant, has been renewed due to the elucidation of the endocannabinoid system and diverse other receptor targets involved in biological cannabinoid effects. The present study therefore investigates the impact of THC on the migration of mesenchymal stem cells (MSCs) which are known to be involved in various regenerative processes such as bone healing. Using Boyden chamber assays, THC was found to increase the migration of adipose-derived MSCs...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285108/elevation-of-arachidonoylethanolamide-levels-by-activation-of-the-endocannabinoid-system-protects-against-colitis-and-ameliorates-remote-organ-lesions-in-mice
#20
Xiaolin Zhao, Peng Liang, Jin Liu, Haixia Jiang, Xiaoshuai Fan, Guo Chen, Cheng Zhou
The endocannabinoid system (ECS) is a potential pharmaceutical target for the treatment of inflammatory bowel diseases (IBDs). The aim of this study was to explore the effects of activation of the ECS on IBD and the associated neural inflammation-induced disruption of the blood-brain barrier (BBB). In a mouse model of trinitrobenzene sulfonic acid-induced colitis, the inhibition of fatty acid amide hydrolase with URB597 elevated the arachidonoylethanolamide concentration of the colon. Macroscopic alterations of the colons were evaluated, and the 7-day survival rate of mice was analyzed...
December 2017: Experimental and Therapeutic Medicine
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