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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acylethanolamides are endogenous compounds with lipid structure including anandamide (AEA), palmitoilethanolamide, oleylamide and oleylethanolamide (OEA). AEA binds to the cannabinoid receptor CB1, located at the central nervous system, while OEA is an endogenous ligand for the alpha subtype of peroxisome-proliferator activating receptor (PPARalpha). Since AEA acts on the same receptor which binds marihuana active derivatives, this group of compounds were called endocannabinoids. Besides typical central effects of cannabinoids, CB1 receptor activation leads to hyperphagia, whereas its pharmacological blockade is followed by changes in energy metabolism favouring substrate oxidation. OEA has inhibitory effects on food intake by acting on PPARalpha receptors which modulate the autonomous nervous system. Both acylethanolamides, AEA and OEA, have opposite effects suggesting that they form part of a satiety sensor system. Whereas fasting triggers AEA release and inhibits OEA synthesis, eating has the reverse effect. Additionally OEA is also produced by adipocytes ad has some effects on lipid metabolism. All these data suggest a role for acylethanolamides and the endocannabinoid system in the pathophysiology of obesity, diabetes and atherosclerosis.
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PMID:[The endocannabinoid system and food intake control]. 1538 9

Cannabinoid (CB)(1) receptors are present throughout the nervous system, including several areas implicated in the control of food intake. Central and peripheral administration of CB(1) agonists increase food intake while CB(1) receptor antagonists reduce food intake. However, in some previous studies, tolerance to the anorectic effects of CB(1) antagonists develops within days. To further delineate the role of endogenous cannabinoid signaling in energy intake, we studied the effects of the CB(1) antagonist AM 251 (1.25, 2.5 and 5 mg/kg ip), the anandamide membrane transporter inhibitor VDM 11 (10 mg/kg ip), and the CB(1) agonists anandamide (1 mg/kg ip), and methanandamide (1 mg/kg ip), on food intake. A single administration of the CB(1) antagonist AM 251 significantly reduced food intake for a total of 6 days (P<.05). Reductions in food intake brought about by AM 251 were accompanied by reductions in weight gain for 6 days (P<.05). Contrary to expectations, VDM 11 did not increase food intake in this study. Anandamide was also unable to increase food intake; however, the more stable agonist methanandamide significantly increased food intake 3 h after administration (P<.05). These results support the role of CB(1) receptor antagonists in the treatment of obesity and suggest that the anorectic effect of AM 251 may last longer than previously reported.
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PMID:Cannabinoid (CB)1 receptor antagonist, AM 251, causes a sustained reduction of daily food intake in the rat. 1545 51

An endogenous compound that binds to the same receptor sites activated by the main psychoactive constituent of marihuana, delta 9 tetrahydrocannabinol (THC), is synthetised in the brain and in several peripheral tissues. The endogenous cannabinoid was named anandamide on the basis of the sanscrit word ananda, that means bringer of inner bliss . Anandamide reproduces marihuana effects,is synthetised in response to physical activity, and is involved in neurobiologic mechanisms common to drug addiction. Cannabinoid CB1 receptors, and their endogenous ligands, are present in brain areas linked to reward circuits. The blockade of CB1 receptors causes anorexia and is being employed to treat obesity. On the contrary, activation of CB1 receptors has appetite stimulant, antiemetic and analgesic properties, that deserve to be studied for putative therapeutical uses.
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PMID:[Endocannabinoids: the inside plant]. 1735 19

Anandamide and oleoylethanolamide (OEA) are lipid mediators that regulate feeding and lipid metabolism. While anandamide, a cannabinoid CB1 receptor agonist, promotes feeding and lipogenesis, oleoylethanolamide, an endogenous agonist of peroxisome proliferator activated receptor alpha (PPAR-alpha), decreases food intake and activates lipid mobilization and oxidation. The treatment with a cannabinoid CB1 receptor antagonist results in reduction of body weight gain and cholesterol in obese humans and rodents. In the present study, we show the benefits of the treatment of obese Zucker rats with a combination of a cannabinoid CB1 receptor antagonist (Rimonabant) and oleoylethanolamide. This combinational therapy improved the separate effects of Rimonabant and OEA, and resulted in marked decreases on feeding, body weight gain, and plasma cholesterol levels. Additionally, the treatment with both drugs reduced the hepatic steatosis observed in Zucker rats, decreasing liver fat deposits and damage, as revealed by the levels of alanine aminotransferase activity in serum. The combined treatment inhibits the expression of stearoyl coenzyme-A desaturase-1 (SCD-1), a pivotal enzyme in lipid biosynthesis and triglyceride mobilization that is linked to obesity phenotypes. These results support the use of combined therapies with cannabinoid CB1 receptor antagonists and PPAR-alpha agonists for the treatment of obesity associated with dyslipemia.
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PMID:The cannabinoid CB1 receptor antagonist SR141716A (Rimonabant) enhances the metabolic benefits of long-term treatment with oleoylethanolamide in Zucker rats. 1746 48

The endocannabinoid (EC) system is a physiological system with an important regulatory role in numerous biological functions, both centrally and peripherally. In certain conditions it can become hyperactive and induce a variety of disorders. The system has two receptor types, designated CB1 and CB2 (present respectively in the CNS and the periphery), as well as endogenous ligands (AEA and 2-AG) and equipment for transporting, synthesizing and degrading them. The discovery of specific CB1 antagonists has opened up interesting new possibilities for the treatment of obesity, diabetes and cardiometabolic risk factors.
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PMID:[Pharmacology of cannabinoid receptors]. 1822 47

Fatty acids ethanolamides (FAEs) are a family of lipid mediators. A member of this family, anandamide, is an endogenous ligand for cannabinoid receptors targeted by the marijuana constituent Delta-9-tetrahydrocannabinol. Anandamide is now established as a brain endocannabinoid messenger and multiple roles for other FAEs have also been proposed. One emerging function of these lipid mediators is the regulation of feeding behavior and body weight. Anandamide causes overeating in rats because of its ability to activate cannabinoid receptors. This action is of therapeutic relevance: cannabinoid agonists are currently used to alleviate anorexia and nausea in AIDS patients, whereas the cannabinoid receptor CB1 antagonist rimonabant was recently found to be effective in the treatment of obesity. In contrast to anandamide, its monounsatured analogue, oleoylethanolamide (OEA), decreases food intake and body weight gain through a cannabinoid receptor-independent mechanism. In the rat proximal small intestine, endogenous OEA levels decrease during fasting and increase upon refeeding. These periprandial fluctuations may represent a previously undescribed signal that modulates between-meal satiety. Pharmacological studies have shown, indeed, that, as a drug, OEA produces profound anorexiant effects in rats and mice, due to selective prolongation of feeding latency and post-meal interval. The effects observed after chronic administration of OEA to different animal models of obesity, clearly indicate that inhibition of eating is not the only mechanism by which OEA can control energy metabolism. In fact, stimulation of lipolysis is responsible for the reduced fat mass and decrease of body weight gain observed in these models. Although OEA may bind to multiple receptors, several lines of evidence indicate that peripheral PPAR-alpha mediates the effects of this compound. The pathophysiological significance of OEA in the regulation of eating and body weight is further evidenced by preliminary clinical results, showing altered levels of this molecule in the cerebrospinal fluid and plasma of subjects recovered from eating disorders. These results complete previous observation on anandamide content, which resulted altered in plasma of women affected by anorexia nervosa or binge-eating disorder.
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PMID:Role of endocannabinoids and their analogues in obesity and eating disorders. 1901 63

The role played by the endocannabinoid system in the regulation of energy balance is currently generating a great amount of interest among several groups of investigators. This interest in large part comes from the urgent need to develop anti-obesity and anti-cachexia drugs around target systems (such as the endocannabinoid system), which appears to be genuinely involved in energy balance regulation. When activated, the endocannabinoid system favors energy deposition through increasing energy intake and reducing energy expenditure. This system is activated in obesity and following food deprivation, which further supports its authentic function in energy balance regulation. The cannabinoid receptor type 1 (CB1), one of the two identified cannabinoid receptors, is expressed in energy-balance brain structures that are also able to readily produce or inactivate N-arachidonoyl ethanolamine (anandamide) and 2-arachidonoylglycerol (2AG), the most abundantly formed and released endocannabinoids. The brain action of endocannabinoid system on energy balance seems crucial and needs to be delineated in the context of the homeostatic and hedonic controls of food intake and energy expenditure. These controls require the coordinated interaction of the hypothalamus, brainstem and limbic system and it appears imperative to unravel those interplays. It is also critical to investigate the metabolic endocannabinoid system while considering the panoply of functions that the endocannabinoid system fulfills in the brain and other tissues. This article aims at reviewing the potential mechanisms whereby the brain endocannabinoid system influences the regulation energy balance.
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PMID:The brain endocannabinoid system in the regulation of energy balance. 1928 58

Anandamide (arachidonoyl ethanol amide, AEA) is an endocannabinoid, acting on CB1 and CB2 receptors. Elevated plasma AEA concentrations in humans have been associated amongst others with obesity, psychological disorders and miscarriage. The occurrence in human plasma of ethanol amides of other unsaturated and saturated fatty acids, including oleic acid and palmitic acid, has also been reported. Most data available on anandamide and other fatty acid ethanol amides (FAEA) until now have been generated by using the LC-MS/MS methodology. Here, we describe a stable-isotope dilution GC-MS/MS method for the quantitative determination of AEA, oleic acid ethanol amide (OEA) and palmitic acid ethanol amide (PEA) in human plasma using their stable-isotope labeled analogs as internal standards. Other FAEA were found in plasma and their concentration was estimated. The present method involves a single solvent extraction of FAEA and their internal standards from plasma (50-1000 microl) with toluene, derivatization to the pentafluorobenzamide pentafluoropropionyl derivatives (FAEA-PFBz-PFP), and simultaneous quantification by selected reaction monitoring of the carboxylate anions produced by collision-induced dissociation of the parent ions [M-PFBz](-). The present method was fully validated for anandamide. Thus, accuracy and imprecision of the method were within the range of 100+/-20% and less than 20%, respectively, in the range investigated (0-4 nM). Mean overall recovery was 90+/-3%. The LOQ and LOD values of the method were determined to be 0.25 nM of added AEA in plasma samples and 400 amol of injected AEA-PFBz-PFP derivative, respectively. In plasma of 16 healthy individuals AEA concentration was measured to be 1.35+/-0.32 nM. This finding is concordant to literature AEA plasma concentrations as measured by LC-MS/MS. The plasma concentrations of OEA, PEA and other FAEA are higher than that of AEA. This GC-MS/MS method is straightforward, accurate, precise, highly specific for FAEA and useful in basic and clinical research.
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PMID:Targeted stable-isotope dilution GC-MS/MS analysis of the endocannabinoid anandamide and other fatty acid ethanol amides in human plasma. 1941 83

The discovery of the endocannabinoid signalling system, that is, of cannabinoid receptors, their endogenous ligands, known as endocannabinoids, and of endocannabinoid anabolic and catabolic enzymes, raised several questions regarding the physiopathological role of these mediators. Several of these questions were answered by investigating alterations in the levels of the most studied endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), in tissues of animal models of disorders, and in bioptic samples and biological fluids (cerebrospinal fluid and blood) of human volunteers. Subsequently, the pharmacological effects of synthetic compounds that selectively target the cannabinoid CB(1) and CB(2) receptors, and endocannabinoid anabolic and catabolic enzymes, established cause-effect relationships between pathological alterations in endocannabinoid levels and the symptoms and progress of several disorders, including emesis, obesity, metabolic disorders, hepatic diseases, pain, inflammation and neurological and neuropsychiatric disorders. These new developments are discussed in this second review on the endocannabinoids, together with the results of pre-clinical and clinical studies on the potential therapeutic use of plant-derived cannabinoids and synthetic agents that manipulate pharmacologically the action at cannabinoid receptors or the tissue levels of AEA and 2-AG.
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PMID:From endocannabinoid profiling to 'endocannabinoid therapeutics'. 1949 79

Anandamide (N-arachidonoylethanolamine, AEA) or its metabolites participate in energy balance mainly through feeding modulation. In addition, AEA has been found to increase 3T3-L1 adipocyte differentiation process. In this study, the effect of AEA, R(+)-methanandamide (R(+)-mAEA), URB597, and indomethacin on primary rat adipocyte differentiation was evaluated by a flow cytometry method and by Oil Red-O staining. Reverse transcription-PCR and western blotting analysis were performed in order to study the effect of AEA on peroxisome proliferator-activated receptor (PPAR)gamma2, cannabinoid receptors (CBRs), fatty acid amidohydrolase (FAAH), and cyclooxygenase-2 (COX-2) expression, during the differentiation process. AEA increased adipocyte differentiation in primary cell cultures in a concentration- and time-dependent manner and induced PPARgamma2 gene expression, confirming findings with 3T3-L1 cell line. CB1R, FAAH, and COX-2 expression was also increased while CB2R expression was decreased. Inhibition of FAAH and COX-2 attenuated the AEA-induced differentiation. Our findings indicate that AEA regulates energy homeostasis not only by appetite modulation but may also regulate adipocyte differentiation and phenotype.
Obesity (Silver Spring) 2009 Oct
PMID:Anandamide increases the differentiation of rat adipocytes and causes PPARgamma and CB1 receptor upregulation. 1954 11


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