anandamide and Anorexia-Nervosa

In this overview we have summarized some aspects of our published work related to the effects of the endocannabinoid system on appetite and suckling. As noted also by several other groups we have found that anandamide, a major endocannabinoid, enhances appetite in mice. On partial or full food deprivation over 24 h the levels of 2-arachidonoyl glycerol (2-AG), a second major cannabinoid, are initially elevated in mouse brain; however, partial food deprivation over a longer period causes reduction of 2-AG levels. Blocking the endocannabinoid system with a CB1 antagonist on the 1st day after birth leads to inhibition of suckling; later administration also affects suckling, but does not fully block it.

Topics: Animals; Animals, Suckling; Anorexia Nervosa; Appetite Regulation; Arachidonic Acids; Cannabinoid Receptor Modulators; Endocannabinoids; Feeding Behavior; Food Deprivation; Glycerides; Humans; Mammals; Mice; Polyunsaturated Alkamides; Receptor, Cannabinoid, CB1

Topics: Amides; Animals; Anorexia Nervosa; Arachidonic Acids; Dietary Fats; Dietary Supplements; Endocannabinoids; Ethanolamines; Feeding Behavior; Humans; Lipids; Oleic Acids; Palmitic Acids; Polyunsaturated Alkamides; Rats; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2

A dysregulation of reward mechanisms was suggested in the pathophysiology of anorexia nervosa (AN), but the role of the endogenous mediators of reward has been poorly investigated. Endocannabinoids, including anandamide and 2-arachidonoylglycerol, and the endocannabinoid-related compounds oleoylethanolamide and palmitoylethanolamide modulate food-related and unrelated reward. Hedonic eating, which is the consumption of food just for pleasure and not homeostatic need, is a suitable paradigm to explore food-related reward.. We investigated responses of endocannabinoids and endocannabinoid-related compounds to hedonic eating in AN.. Peripheral concentrations of anandamide, 2-arachidonoylglycerol, oleoylethanolamide, and palmitoylethanolamide were measured in 7 underweight and 7 weight-restored AN patients after eating favorite and nonfavorite foods in the condition of no homeostatic needs, and these measurements were compared with those of previously studied healthy control subjects.. 1) In healthy controls, plasma 2-arachidonoylglycerol concentrations decreased after both types of meals but were significantly higher in hedonic eating; in underweight AN patients, 2-arachidonoylglycerol concentrations did not show specific time patterns after eating either favorite or nonfavorite foods, whereas in weight-restored patients, 2-arachidonoylglycerol concentrations showed similar increases with both types of meals. 2) Anandamide plasma concentrations exhibited no differences in their response patterns to hedonic eating in the groups. 3) Compared with 2-arachidonoylglycerol, palmitoylethanolamide concentrations exhibited an opposite response pattern to hedonic eating in healthy controls; this pattern was partially preserved in underweight AN patients but not in weight-restored ones. 4) Like palmitoylethanolamide, oleoylethanolamide plasma concentrations tended to be higher in nonhedonic eating than in hedonic eating in healthy controls; moreover, no difference between healthy subjects and AN patients was observed for food-intake-induced changes in oleoylethanolamide concentrations.. These data confirm that endocannabinoids and endocannabinoid-related compounds are involved in food-related reward and suggest a dysregulation of their physiology in AN. This trial was registered at ISRCTN.org as ISRCTN64683774.

Topics: Adolescent; Adult; Amides; Anorexia Nervosa; Arachidonic Acids; Case-Control Studies; Endocannabinoids; Energy Intake; Ethanolamines; Female; Glycerides; Healthy Volunteers; Humans; Male; Meals; Oleic Acids; Palmitic Acids; Polyunsaturated Alkamides; Retrospective Studies; Reward; Thinness; Young Adult

Endocannabinoids, anandamide, and 2-arachidonoyl glycerol are involved in food intake and appetite. Although anandamide is now thought to be a ligand for vanilloid receptor, receptors that are targets of anandamide could play a similar role in eating behaviors and related disorders. This study therefore focused on the receptor, which is called G-protein-coupled receptor 55 (GPR55) that had recently been reported to have binding affinity for endocannabinoids. Functional analysis of the sole missense polymorphism, rs3749073 (Gly195Val) in the GPR55 gene was performed by detecting the phosphorylation level of extracellular signal-regulated kinase (ERK) in Chinese-Hamster-Ovary (CHO) cells engineered to express human GPR55. Val195 type GPR55 appeared to induce less phosphorylated ERK than Gly195 type GPR55 when CHO cells were treated with anandamide and lysophosphatidylinositol (LPI). An association between the functional Gly195Val polymorphism and anorexia nervosa was tested in a female Japanese population comprising 235 patients and 1244 controls. The Val195 allele and homozygote of the Val195 allele were more abundant in the group of patients diagnosed with anorexia nervosa (P = 0.023, Odds ratio = 1.31 (95% Cl = 1.03-1.37), P = 0.0048, OR = 2.41 (95% Cl = 1.34-4.34), respectively). In conclusion, the low-functioning Val195 allele of GPR55 appears to be a risk factor for anorexia nervosa.

Topics: Adolescent; Adult; Animals; Anorexia Nervosa; Arachidonic Acids; Calcium Channel Blockers; CHO Cells; Cricetinae; Cricetulus; Dose-Response Relationship, Drug; Endocannabinoids; Enzyme-Linked Immunosorbent Assay; Extracellular Signal-Regulated MAP Kinases; Female; Gene Frequency; Genome-Wide Association Study; Genotype; Glycine; Humans; Japan; Personality Inventory; Phosphorylation; Polymorphism, Genetic; Polyunsaturated Alkamides; Receptors, Cannabinoid; Receptors, G-Protein-Coupled; Transfection; Valine; Young Adult