n-oleoylethanolamine and linoleoyl-ethanolamide

Anandamide is a well-known agonist for the cannabinoid receptors. Along with endogenous anandamide other non-endocannabinoid N-acylethanolamines are also formed, apparently in higher amounts. These include mainly oleoylethanolamide (OEA), palmitoyelethanolamide (PEA) and linoleoylethanolamide (LEA), and they have biological activity by themselves being anorectic and anti-inflammatory. It appears that the major effect of dietary fat on the level of these molecules is in the gastrointestinal system, where OEA, PEA and LEA in the enterocytes may function as homeostatic signals, which are decreased by prolonged consumption of a high-fat diet. These lipid amides appear to mediate their signaling activity via activation of PPARα in the enterocyte followed by activation of afferent vagal fibers leading to the brain. Through this mechanism OEA, PEA and LEA may both reduce the consumption of a meal as well as increase the reward value of the food. Thus, they may function as homeostatic intestinal signals involving hedonic aspects that contribute to the regulation of the amounts of dietary fat to be ingested.

Topics: Amides; Animals; Appetite; Dietary Fats; Endocannabinoids; Enterocytes; Ethanolamines; Humans; Intestines; Linoleic Acids; Oleic Acids; Palmitic Acids; Polyunsaturated Alkamides

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

Animal data suggest that dietary fat composition may influence endocannabinoid (EC) response and dietary behavior. This study tested the hypothesis that fatty acid composition of a meal can influence the short-term response of ECs and subsequent energy intake in humans. Fifteen volunteers on three occasions were randomly offered a meal containing 30 g of bread and 30 mL of one of three selected oils: sunflower oil (SO), high oleic sunflower oil (HOSO) and virgin olive oil (VOO). Plasma EC concentrations and appetite ratings over 2 h and energy intake over 24 h following the experimental meal were measured. Results showed that after HOSO and VOO consumption the circulating oleoylethanolamide (OEA) was significantly higher than after SO consumption; a concomitantly significant reduction of energy intake was found. For the first time the oleic acid content of a meal was demonstrated to increase the post-prandial response of circulating OEA and to reduce energy intake at subsequent meals in humans.

Topics: Adult; Amides; Appetite Regulation; Breakfast; Cross-Over Studies; Diet Records; Endocannabinoids; Energy Intake; Ethanolamines; Female; Humans; Italy; Linoleic Acids; Male; Oleic Acid; Oleic Acids; Olive Oil; Palmitic Acids; Plant Oils; Polyunsaturated Alkamides; Postprandial Period; Sunflower Oil; Young Adult

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

Alarcón-Yaquetto, Dulce E., Lidia Caballero, and Gustavo F. Gonzales. Association between plasma N-acylethanolamides and high hemoglobin concentration in Southern Peruvian highlanders. High Alt Med Biol 18:322-329, 2017.-High-altitude (HA) hypoxia is a stressful condition endured by organisms through different mechanisms. Failing to adapt to chronic HA exposure leads to a disease called chronic mountain sickness (CMS) characterized by excessive erythrocytosis (hemoglobin [Hb] ≥19 g/dL for women and ≥21 g/dL for men). Genes encoding for peroxisome proliferator-activated receptor (PPAR) subunits α and γ have been proposed as candidate genes for HA adaptation. N-acylethanolamides (NAEs) are endogenous fatty acid substances that bind to PPAR-α and -γ. NAEs are also able to modulate the endocannabinoid system, a signaling pathway activated in physiological stressful conditions. In the frame of a metabolomic study, we measured plasma levels of four NAEs: palmitoylethanolamide (PEA), oleoylethanolamide (OEA), stearoyl ethanolamide (SEA), and linoleoyl ethanolamide (LEA) in natives from Puno (3830 m), a city located in the Peruvian Southern Andes, and Lima (150 m). All NAEs were significantly higher in the HA population (p < 0.001, q < 0.001). Subjects with higher NAE values were those with higher Hb concentration and lower pulse oxygen saturation. However, there was no association between NAEs and CMS score. Our results suggest that PEA and OEA could be involved in physiological regulation following long-term HA exposure.

Topics: Adult; Altitude; Altitude Sickness; Amides; Chronic Disease; Endocannabinoids; Ethanolamines; Fatty Acids; Female; Hemoglobins; Humans; Hypoxia; Indians, South American; Linoleic Acids; Male; Oleic Acids; Oxygen; Palmitic Acids; Peru; Polyunsaturated Alkamides; Stearic Acids