anandamide and linoleoyl-ethanolamide

Anandamide and the other N-acylethanolamines, e.g. oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and linoleoylethanolamide (LEA), may be formed by several enzymatic pathways from their precursors, which are the N-acylated ethanolamine phospholipids. The exact enzymatic pathways involved in their biosynthesis in specific tissues are not clarified. It has been suggested that endogenous anandamide could stimulate food intake by activation of cannabinoid receptors in the brain and/or in the intestinal tissue. On the other hand, endogenous OEA and PEA have been suggested to inhibit food intake by acting on receptors in the intestine. At present, there is no clear role for endogenous anandamide in controlling food intake via cannabinoid receptors, neither centrally nor in the gastrointestinal tract. However, OEA, PEA and perhaps also LEA may be involved in regulation of food intake by selective prolongation of feeding latency and post-meal interval. These N-acylethanolamines seem to be formed locally in the intestine, where they can activate PPARalpha located in close proximity to their site of synthesis. The rapid onset of OEA response and its reliance on an intact vagus nerve suggests that activation of PPARalpha does not result in formation of a transcription-dependent signal but must rely on an unidentified non-genomic signal that translates to activation of vagal afferents. Whether GPR119, TRPV1 and/or intestinal ceramide levels also contribute to the anorectic and weight-reducing effect of exogenous OEA is less clear. Prolonged intake of dietary fat (45 energy%) may promote over-consumption of food by decreasing the endogenous levels of OEA, PEA and LEA in the intestine.

Topics: Animals; Arachidonic Acids; Dietary Fats; Eating; Endocannabinoids; Ethanolamines; Fats; Linoleic Acids; Oleic Acids; Polyunsaturated Alkamides; Receptors, Cannabinoid

Food palatability increases food intake and may lead to overeating. The mechanisms behind this observation are still largely unknown.. The aims of this study were the following: 1) to elucidate the plasma responses of endocannabinoids, N-acylethanolamines, and gastrointestinal peptides to a palatable (sweet), unpalatable (bitter), and sensory-acceptable (tasteless control) food, and 2) to verify whether some of these bioactive compounds can serve as plasma biomarkers of food liking in humans.. Three puddings providing 60 kcal (35% from proteins, 62% from carbohydrates, and 3% from fats) but with different taste were developed. Twenty healthy subjects (11 women and 9 men; mean age 28 y and BMI 22.7 kg/m(2)), selected because they liked the puddings in the order sweet > control > bitter, participated in a randomized crossover study based on a modified sham feeding (MSF) protocol. Blood samples at baseline and every 5 min up to 20 min after the MSF were analyzed for gastrointestinal peptides, endocannabinoids, and N-acylethanolamines. Thirty minutes after the MSF, energy intake at an ad libitum breakfast was measured.. After the MSF, no response was observed in 7 of 9 gastrointestinal peptides measured. The plasma ghrelin concentration at 20 min after the sweet and bitter puddings was 25% lower than after the control pudding (P = 0.04), and the pancreatic polypeptide response after the sweet pudding was 23% greater than after the bitter pudding (P = 0.02). The plasma response of 2-arachidonoylglycerol after the sweet pudding was 37% and 15% higher than after the bitter (P < 0.001) and control (P = 0.03) puddings, respectively. Trends for greater responses of anandamide (P = 0.06), linoleoylethanolamide (P = 0.07), palmitoylethanolamide (P = 0.06), and oleoylethanolamide (P = 0.09) were found after the sweet pudding than after the bitter pudding. No differences in subsequent energy intake were recorded.. The data demonstrated that food palatability influenced some plasma endocannabinoid and N-acylethanolamine concentrations during the cephalic phase response and indicated that 2-arachidonoylglycerol and pancreatic polypeptide can be used as biomarkers of food liking in humans.

Topics: Adult; Amides; Arachidonic Acids; Blood Glucose; Body Mass Index; Cross-Over Studies; Edetic Acid; Endocannabinoids; Energy Intake; Ethanolamines; Female; Food Preferences; Ghrelin; Glycerides; Humans; Linear Models; Linoleic Acids; Male; Oleic Acids; Palmitic Acids; Pancreatic Polypeptide; Polyunsaturated Alkamides; Taste; Young Adult

The endocannabinoid system plays a substantial role in analgesia.. To analyze N-arachidonoylethanolamine (AEA), N-oleoylethanolamine (OEA), linoleoyl ethanolamide (LEA), α-linoleoyl ethanolamine (α-LNEA), N-palmitoylethanolamine (PEA) and N-stearoyl ethanolamine (SEA) in two groups of patients having chronic pancreatic diseases.. Twenty-six patients with chronic pancreatitis, 26 patients with pancreatic ductal adenocarcinoma and 36 healthy subjects were studied. The visual analogic scale (VAS) was used for assessing pain immediately before the venipuncture to obtain blood in all subjects. Six endocannabinoids were measured in serum of the patients enrolled.. Only OEA, LEA and PEA serum levels were significantly higher in patients with pain as compared to those without. Using the cutoff values, the sensitivity and specificity of the various endocannabinoids in evaluating pain in patients with chronic pancreatitis and in those with pancreatic ductal adenocarcinoma were: 44.2% and 95.6% for AEA, 83.7% and 73.3% for LEA, 88.4% and 91.1% for LNEA, 81.4% and 82.2% for OEA, 81.4% and 88.9% for PEA, 86.0% and 88.9% for SEA, respectively.. Endocannabinoids are not useful in assessing pain in patients with chronic pancreatic diseases and they cannot replace a simple method such as VAS for assessing the pain and its intensity.

Topics: Abdominal Pain; Adolescent; Adult; Aged; Aged, 80 and over; Amides; Arachidonic Acids; Cancer Pain; Carcinoma, Pancreatic Ductal; Case-Control Studies; Endocannabinoids; Ethanolamines; Female; Humans; Linoleic Acids; Male; Middle Aged; Oleic Acids; Pain Measurement; Palmitic Acids; Pancreatic Neoplasms; Pancreatitis, Chronic; Polyunsaturated Alkamides; Predictive Value of Tests; ROC Curve; Stearic Acids; Young Adult

We describe and validate a sensitive UHPLC-ESI-QTOF-MS method for the simultaneous quantification of seven endocannabinoids and non-endocannabinoids related N-acylethanolamides: N-arachidonoylethanolamide, N-palmitoylethanolamide, N-stearoylethanolamide, N-oleoylethanolamide, N-linoleoylethanolamide, N-α-linolenoylethanolamide and N-eicosapentaenoylethanolamide in several bio-matrices for the purpose of research and clinical application. We examined effects of different liquid-liquid and solid phase extraction on the recovery of endocannabinoids and N-acylethanolamides. Protein precipitation with cooled acetone and extraction with acetonitrile (1% v/v formic acid) using OASIS HLB cartridge gave better results. Separation was performed on a Waters Acquity UPLC HSST3 column using a 9min elution gradient coupled with high resolution mass spectrometry (QTOF/MS). The high sensitivity of the developed method allow its application on sample with low volumes or low levels of endocannabinoids and N-acylethanolamides and make the method suitable for routine measurement in human bio-matrices, such as plasma, serum (500μL), urine (1mL) and tissues (10-30mg). Its application in clinical research could contribute to unravel pathophysiological roles of these family of lipid mediators and disclose novel diagnostic and prognostic markers.

Topics: Amides; Animals; Arachidonic Acids; Chromatography, High Pressure Liquid; Endocannabinoids; Ethanolamines; Humans; Limit of Detection; Linoleic Acids; Male; Palmitic Acids; Polyunsaturated Alkamides; Rats; Spectrometry, Mass, Electrospray Ionization; Stearic Acids; Tandem Mass Spectrometry

A sensitive and selective liquid chromatography tandem mass spectrometry (LC\\MS\\MS) method has been developed for the simultaneous quantification in human plasma of the endocannabinoid anandamide (AEA) and three other related ethanolamides, linoleoyl ethanolamide (LEA), oleoyl ethanolamide (OEA), and palmitoyl ethanolamide (PEA). The analytical methodology requires 50 microL of human plasma which is processed via protein precipitation using a 96-well protein precipitation plate. Chromatographic separation of plasma extract was achieved with a Phenomenex Gemini C6-Phenyl HPLC column (2.1 mm x 50 mm, 5 microm) at a flow rate of 0.30 mL/min using gradient elution and a mobile phase consisting of acetonitrile and 5 mM ammonium formate. All four fatty acid ethanolamides were quantified by positive ion electrospray ionization tandem mass spectrometry, with the detection of ion current signal generated from the selected reaction monitoring (SRM) transition of [M+H](+)-->m/z 62. Deuterated anandamide (AEA-d8) was used as an internal standard for all four ethanolamides. The lower limit of quantitation was 0.05 ng/mL for AEA and LEA, 0.5 ng/mL for OEA and 1.0 ng/mL for PEA. Inter-assay precision and accuracy were typically within 12% for the four endogenous analytes and overall extraction recoveries ranged between 40% and 100%.

Topics: Arachidonic Acids; Cannabinoid Receptor Modulators; Chromatography, High Pressure Liquid; Endocannabinoids; Humans; Linoleic Acids; Polyunsaturated Alkamides; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Amides; Animals; Arachidonic Acid; Arachidonic Acids; Cyclic AMP; Dinoprostone; Endocannabinoids; Enzyme Activation; Ethanolamines; Genistein; GTP-Binding Proteins; Linoleic Acids; Macrophages; Mice; Naphthalenes; Neuroblastoma; Nitriles; Palmitic Acids; Phospholipases A; Polyunsaturated Alkamides; Second Messenger Systems; Staurosporine; Tumor Cells, Cultured; Tyrphostins; Virulence Factors, Bordetella