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Cannabinoid receptor and fatty acid oxidation

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https://www.readbyqxmd.com/read/27672360/glucagon-like-peptide-1-excites-firing-and-increases-gabaergic-miniature-postsynaptic-currents-mpscs-in-gonadotropin-releasing-hormone-gnrh-neurons-of-the-male-mice-via-activation-of-nitric-oxide-no-and-suppression-of-endocannabinoid-signaling-pathways
#1
Imre Farkas, Csaba Vastagh, Erzsébet Farkas, Flóra Bálint, Katalin Skrapits, Erik Hrabovszky, Csaba Fekete, Zsolt Liposits
Glucagon-like peptide-1 (GLP-1), a metabolic signal molecule, regulates reproduction, although, the involved molecular mechanisms have not been elucidated, yet. Therefore, responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the GLP-1 analog Exendin-4 and elucidation of molecular pathways acting downstream to the GLP-1 receptor (GLP-1R) have been challenged. Loose patch-clamp recordings revealed that Exendin-4 (100 nM-5 μM) elevated firing rate in hypothalamic GnRH-GFP neurons of male mice via activation of GLP-1R...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27516570/metabolism-of-endocannabinoids
#2
Michał Biernacki, Elżbieta Skrzydlewska
Endocannabinoids belong to a group of ester, ether and amide derivatives of fatty acids, which are endogenous ligands of receptors CB1, CB2, TRPV1 and GPR55 that are included in the endocannabinoid system of the animal organism. The best known endocannabinoids are: N-arachidonylethanolamide called anandamide (AEA) and 2-arachidonoylglycerol (2-AG). They occur in all organisms, and their highest level is observed in the brain. In this review the mechanisms of synthesis and degradation of both AEA and 2-AG are shown...
2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/26847930/cannabinoid-receptor-type-1-mediates-high-fat-diet-induced-insulin-resistance-by-increasing-forkhead-box-o1-activity-in-a-mouse-model-of-obesity
#3
Chin-Chang Chen, Tzung-Yan Lee, Ching-Fai Kwok, Yung-Pei Hsu, Kuang-Chung Shih, Yan-Jie Lin, Low-Tone Ho
Hepatic glucose production is promoted by forkhead box O1 (FoxO1) under conditions of insulin resistance. The overactivity of cannabinoid receptor type 1 (CB1R) partly causes increased liver fat deposits and metabolic dysfunction in obese rodents by decreasing mitochondrial function. The aim of the present study was to investigate the role of FoxO1 in CB1R-mediated insulin resistance through the dysregulation of mitochondrial function in the livers of mice with high-fat diet (HFD)-induced obesity. For this purpose, male C57BL/6 mice were randomly assigned to groups and either fed a standard diet (STD), a HFD, or a HFD with 1-week treatment of the CB1R inverse agonist, AM251, at 1 or 5 mg/kg...
March 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/26806592/interactions-between-dietary-oil-treatments-and-genetic-variants-modulate-fatty-acid-ethanolamides-in-plasma-and-body-weight-composition
#4
RANDOMIZED CONTROLLED TRIAL
Shuaihua Pu, Peter Eck, David J A Jenkins, Philip W Connelly, Benoît Lamarche, Penny M Kris-Etherton, Sheila G West, Xiaoran Liu, Peter J H Jones
Fatty acid ethanolamides (FAE), a group of lipid mediators derived from long-chain fatty acids (FA), mediate biological activities including activation of cannabinoid receptors, stimulation of fat oxidation and regulation of satiety. However, how circulating FAE levels are influenced by FA intake in humans remains unclear. The objective of the present study was to investigate the response of six major circulating FAE to various dietary oil treatments in a five-period, cross-over, randomised, double-blind, clinical study in volunteers with abdominal obesity...
March 28, 2016: British Journal of Nutrition
https://www.readbyqxmd.com/read/26677906/in-vitro-inhibition-and-enhancement-of-liver-microsomal-s-777469-metabolism-by-long-chain-fatty-acids-and-serum-albumin-insight-into-in-vitro-and-in-vivo-discrepancy-of-metabolite-formation-in-humans
#5
Kazutaka Sekiguchi, Takushi Kanazu, Norie Murayama, Hiroshi Yamazaki, Yoshitaka Yamaguchi
1. It was previously demonstrated that 10% of S-777469, a cannabinoid receptor 2 selective agonist, is metabolized to its carboxylic acid metabolite (S-777469 5-carboxylic acid, 5-CA) in humans in vivo, while the formation of 5-CA is extremely low in human cryopreserved hepatocytes and liver microsomes (HLMs). In this study, factors causing the different metabolite formation rates of S-777469 in vitro and in vivo were investigated. 2. Formation of 5-CA and S-777469 5-hydroxymethyl (5-HM), a precursor metabolite of 5-CA, was catalyzed by CYP2C9...
2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/26102932/6b-09-effect-of-cannabinoid-receptor-activation-on-aberrant-mitochondrial-bioenergetics-in-hypertrophied-cardiac-myocytes
#6
Y Lu, H D Anderson
OBJECTIVE: We recently reported that activation of endocannabinoid receptors attenuates cardiac myocyte hypertrophy. Mitochondrial dysfunction has emerged as a critical determinant of aberrant myocyte energy production in cardiac hypertrophy. Thus, we determined endocannabinoid influence on mitochondrial function in the hypertrophied cardiac myocyte. DESIGN AND METHOD: The experimental paradigm of hypertrophy in this study was neonatal rat cardiac myocytes treated with endothelin-1 (ET1; 0...
June 2015: Journal of Hypertension
https://www.readbyqxmd.com/read/26082188/peroxisome-proliferator-activated-receptor-%C3%AE-inhibition-protects-against-doxorubicin-induced-cardiotoxicity-in-mice
#7
Mahdieh Rahmatollahi, Somayeh Mahmoodi Baram, Reza Rahimian, Seyed Soheil Saeedi Saravi, Ahmad Reza Dehpour
Doxorubicin is an effective chemotherapeutic drug against a considerable number of malignancies. However, its toxic effects on myocardium are confirmed as major limit of utilization. PPAR-α is highly expressed in the heart, and its activation leads to an increased cardiac fatty acid oxidation and cardiomyocyte necrosis. This study was performed to adjust the hypothesis that PPAR-α receptor inhibition protects against doxorubicin-induced cardiac dysfunction in mice. Male Balb/c mice were used in this study...
July 2016: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/25422468/overactive-cannabinoid-1-receptor-in-podocytes-drives-type-2-diabetic-nephropathy
#8
Tony Jourdan, Gergő Szanda, Avi Z Rosenberg, Joseph Tam, Brian James Earley, Grzegorz Godlewski, Resat Cinar, Ziyi Liu, Jie Liu, Cynthia Ju, Pál Pacher, George Kunos
Diabetic nephropathy is a major cause of end-stage kidney disease, and overactivity of the endocannabinoid/cannabinoid 1 receptor (CB1R) system contributes to diabetes and its complications. Zucker diabetic fatty (ZDF) rats develop type 2 diabetic nephropathy with albuminuria, reduced glomerular filtration, activation of the renin-angiotensin system (RAS), oxidative/nitrative stress, podocyte loss, and increased CB1R expression in glomeruli. Peripheral CB1R blockade initiated in the prediabetic stage prevented these changes or reversed them when animals with fully developed diabetic nephropathy were treated...
December 16, 2014: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/25392487/a-lipid-gate-for-the-peripheral-control-of-pain
#9
REVIEW
Daniele Piomelli, Andrea G Hohmann, Virginia Seybold, Bruce D Hammock
Cells in injured and inflamed tissues produce a number of proalgesic lipid-derived mediators, which excite nociceptive neurons by activating selective G-protein-coupled receptors or ligand-gated ion channels. Recent work has shown that these proalgesic factors are counteracted by a distinct group of lipid molecules that lower nociceptor excitability and attenuate nociception in peripheral tissues. Analgesic lipid mediators include endogenous agonists of cannabinoid receptors (endocannabinoids), lipid-amide agonists of peroxisome proliferator-activated receptor-α, and products of oxidative metabolism of polyunsaturated fatty acids via cytochrome P450 and other enzyme pathways...
November 12, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/24979612/ligand-activation-of-cannabinoid-receptors-attenuates-hypertrophy-of-neonatal-rat-cardiomyocytes
#10
Yan Lu, Bolanle C Akinwumi, Zongjun Shao, Hope D Anderson
: Endocannabinoids are bioactive amides, esters, and ethers of long-chain polyunsaturated fatty acids. Evidence suggests that activation of the endocannabinoid pathway offers cardioprotection against myocardial ischemia, arrhythmias, and endothelial dysfunction of coronary arteries. As cardiac hypertrophy is a convergence point of risk factors for heart failure, we determined a role for endocannabinoids in attenuating endothelin-1-induced hypertrophy and probed the signaling pathways involved. The cannabinoid receptor ligand anandamide and its metabolically stable analog, R-methanandamide, suppressed hypertrophic indicators including cardiomyocyte enlargement and fetal gene activation (ie, the brain natriuretic peptide gene) elicited by endothelin-1 in isolated neonatal rat ventricular myocytes...
November 2014: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/24937045/the-fatty-acid-amide-hydrolase-inhibitor-pf-3845-promotes-neuronal-survival-attenuates-inflammation-and-improves-functional-recovery-in-mice-with-traumatic-brain-injury
#11
Flaubert Tchantchou, Laura B Tucker, Amanda H Fu, Rebecca J Bluett, Joseph T McCabe, Sachin Patel, Yumin Zhang
Traumatic brain injury (TBI) is the leading cause of death in young adults in the United States, but there is still no effective agent for treatment. N-arachidonoylethanolamine (anandamide, AEA) is a major endocannabinoid in the brain. Its increase after brain injury is believed to be protective. However, the compensatory role of AEA is transient due to its rapid hydrolysis by the fatty acid amide hydrolase (FAAH). Thus, inhibition of FAAH can boost the endogenous levels of AEA and prolong its protective effect...
October 2014: Neuropharmacology
https://www.readbyqxmd.com/read/24864249/endocannabinoid-receptors-gene-expression-in-morbidly-obese-women-with-nonalcoholic-fatty-liver-disease
#12
Teresa Auguet, Alba Berlanga, Esther Guiu-Jurado, Ximena Terra, Salomé Martinez, Carmen Aguilar, Elisa Filiu, Ajla Alibalic, Fàtima Sabench, Mercé Hernández, Daniel Del Castillo, Cristóbal Richart
BACKGROUND: Recent reports suggest a role for the endocannabinoid system in the pathology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship between liver expression of cannabinoid (CB) receptor subtypes, CB1 and CB2, in morbidly obese (MO) women with different histological stages of NAFLD. METHODS: We analysed hepatic CB1 and CB2 mRNA expression, and the expression of genes involved in lipid metabolism in 72 MO women, subclassified by liver histology into MO with normal liver (NL, n = 16), simple steatosis (SS, n = 28), and nonalcoholic steatohepatitis (NASH, n = 28) by enzyme-linked immunosorbent assay and RT-PCR...
2014: BioMed Research International
https://www.readbyqxmd.com/read/24819878/endocannabinoid-regulation-in-human-endometrium-across-the-menstrual-cycle
#13
Jessica G Scotchie, Ricardo F Savaris, Caitlin E Martin, Steven L Young
Humans produce endogenous cannabinoids (endocannabinoids), a group of molecules that activate the same receptors as tetrahydrocannabinol. Endocannabinoids play important roles in reproduction in multiple species, but data in human endometrium are limited. Because endocannabinoids such as anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) often act within tissues as paracrine factors, their effects can be modulated by changes in expression of locally produced synthetic and degradative/oxidative enzymes. The objective of this study was to localize and quantify expression of these key synthetic and degradative/oxidative enzymes for AEA and 2-AG in human endometrium throughout the menstrual cycle...
January 2015: Reproductive Sciences
https://www.readbyqxmd.com/read/24793304/emerging-drugs-for-neuropathic-pain
#14
REVIEW
Ian Gilron, Anthony H Dickenson
INTRODUCTION: Neuropathic pain is a costly and disabling condition, which affects up to 8% of the population. Available therapies often provide incomplete pain relief and treatment-related side effects are common. Preclinical neuropathic pain models have facilitated identification of several promising targets, which have progressed to human clinical phases of evaluation. AREAS COVERED: A systematic database search yielded 25 new molecular entities with specified pharmacological mechanisms that have reached Phase II or III clinical trials...
September 2014: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/24780080/inhibition-of-cox-2-mediated-eicosanoid-production-plays-a-major-role-in-the-anti-inflammatory-effects-of-the-endocannabinoid-n-docosahexaenoylethanolamine-dhea-in-macrophages
#15
Jocelijn Meijerink, Mieke Poland, Michiel G J Balvers, Pierluigi Plastina, Carolien Lute, Jvalini Dwarkasing, Klaske van Norren, Renger F Witkamp
BACKGROUND AND PURPOSE: N-docosahexaenoylethanolamine (DHEA) is the ethanolamine conjugate of the long-chain polyunsaturated n-3 fatty acid docosahexaenoic (DHA; 22: 6n-3). Its concentration in animal tissues and human plasma increases when diets rich in fish or krill oil are consumed. DHEA displays anti-inflammatory properties in vitro and was found to be released during an inflammatory response in mice. Here, we further examine possible targets involved in the immune-modulating effects of DHEA...
January 2015: British Journal of Pharmacology
https://www.readbyqxmd.com/read/24682422/mechanisms-of-endothelium-dependent-relaxation-evoked-by-anandamide-in-isolated-human-pulmonary-arteries
#16
Marta Baranowska-Kuczko, Hanna Kozłowska, Mirosław Kozłowski, Eberhard Schlicker, Monika Kloza, Arkadiusz Surażyński, Emilia Grzęda, Barbara Malinowska
Endocannabinoids contract, relax or do not affect vessels with different calibre and tone in the pulmonary circulation in four species. The aim of the present study was to determine the mechanisms involved in the anandamide-induced relaxation of human pulmonary arteries (hPAs). Studies were performed in the isolated hPAs pre-constricted with the prostanoid TP receptor agonist, U-46619. To detect fatty acid amide hydrolase (FAAH) expression, Western blots were used. Anandamide concentration dependently relaxed the endothelium-intact hPAs pre-constricted with U-46619...
May 2014: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/24548820/cyclooxygenase-metabolism-mediates-vasorelaxation-to-2-arachidonoylglycerol-2-ag-in-human-mesenteric-arteries
#17
Christopher P Stanley, Saoirse E O'Sullivan
OBJECTIVE: The vasorelaxant effect of 2-arachidonoylglycerol (2-AG) has been well characterised in animals. 2-AG is present in human vascular cells and is up-regulated in cardiovascular pathophysiology. However, the acute vascular actions of 2-AG have not been explored in humans. APPROACH: Mesenteric arteries were obtained from patients receiving colorectal surgery and mounted on a myograph. Arteries were contracted and 2-AG concentration-response curves were carried out...
March 2014: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/24397856/n-acylethanolamines-lipid-metabolites-with-functions-in-plant-growth-and-development
#18
REVIEW
Elison B Blancaflor, Aruna Kilaru, Jantana Keereetaweep, Bibi Rafeiza Khan, Lionel Faure, Kent D Chapman
Twenty years ago, N-acylethanolamines (NAEs) were considered by many lipid chemists to be biological 'artifacts' of tissue damage, and were, at best, thought to be minor lipohilic constituents of various organisms. However, that changed dramatically in 1993, when anandamide, an NAE of arachidonic acid (N-arachidonylethanolamine), was shown to bind to the human cannabinoid receptor (CB1) and activate intracellular signal cascades in mammalian neurons. Now NAEs of various types have been identified in diverse multicellular organisms, in which they display profound biological effects...
August 2014: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/24381003/role-of-adiponectin-in-the-metabolic-effects-of-cannabinoid-type-1-receptor-blockade-in-mice-with-diet-induced-obesity
#19
Joseph Tam, Grzegorz Godlewski, Brian J Earley, Liang Zhou, Tony Jourdan, Gergö Szanda, Resat Cinar, George Kunos
The adipocyte-derived hormone adiponectin promotes fatty acid oxidation and improves insulin sensitivity and thus plays a key role in the regulation of lipid and glucose metabolism and energy homeostasis. Chronic cannabinoid type 1 (CB1) receptor blockade also increases lipid oxidation and improves insulin sensitivity in obese individuals or animals, resulting in reduced cardiometabolic risk. Chronic CB1 blockade reverses the obesity-related decline in serum adiponectin levels, which has been proposed to account for the metabolic effects of CB1 antagonists...
February 15, 2014: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/24102214/prostamide-f-2-%C3%AE-receptor-antagonism-combined-with-inhibition-of-faah-may-block-the-pro-inflammatory-mediators-formed-following-selective-faah-inhibition
#20
Alessia Ligresti, Jose Martos, Jenny Wang, Francesca Guida, Marco Allarà, Vittoria Palmieri, Livio Luongo, David Woodward, Vincenzo Di Marzo
BACKGROUND AND PURPOSE: Prostamides are lipid mediators formed by COX-2-catalysed oxidation of the endocannabinoid anandamide and eliciting effects often opposed to those caused by anandamide. Prostamides may be formed when hydrolysis of anandamide by fatty acid amide hydrolase (FAAH) is physiologically, pathologically or pharmacologically decreased. Thus, therapeutic benefits of FAAH inhibitors might be attenuated by concomitant production of prostamide F2 α . This loss of benefit might be minimized by compounds designed to selectively antagonize prostamide receptors and also inhibiting FAAH...
March 2014: British Journal of Pharmacology
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