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Oleoylethanolamide (OEA)

Oleoylethanolamide's anti obesity actions (2017 Oleoylethanolamide A fat ally in the fight

the molecule of satiety

Best reviews

2023: A review of how intestinal homeostasis is regulated by your gut microbiome & oleoylethanolamide
Gut microbiota and oleoylethanolamide in the regulation of intestinal homeostasis

2021: This review looks at how PEA & oleoylethanolamide binds to GPR119 & GPR55 (receptors that may one day be known as CB3 & CB4)

GPR119 and GPR55 as Receptors for Fatty Acid Ethanolamides, Oleoylethanolamide and Palmitoylethanolamide

2020: On oleoylethanolamide for obesity, a review of 30 studies with excellent explanations of the mechanisms
A systematic review of the effects of oleoylethanolamide, a high-affinity endogenous ligand of PPAR-α, on the management and prevention of obesity


2019: A review of OEA for obesity
Oleoylethanolamide: A novel pharmaceutical agent in the management of obesity-an updated review


2018: A review of oleoylethanolamide in eating behavior (good charts)
Oleoylethanolamide: The role of a bioactive lipid amide in modulating eating behaviour

2017: A review with a good chart
Oleoylethanolamide: A fat ally in the fight against obesity

Chart Gallery

Clinical Research

2023: In obese humans with non-alcoholic fatty liver disease, 12 weeks of oleoylethanolamide improved levels of lipids related to metabolism via modulation of genetic expression
Effects of oleoylethanolamide supplementation on the expression of lipid metabolism-related genes and serum NRG4 levels in patients with non-alcoholic fatty liver disease: A randomized controlled trial


2023: In humans undergoing prolonged fasting, they upregulated levels of PEA, oleoylethanolamide, spermidine & 1-methylnicotinamide
Human fasting modulates macrophage function and upregulates multiple bioactive metabolites that extend lifespan in Caenorhabditis elegans: a pilot clinical study

2022: In girls with dysmenorrhea pain, two months of oleoylethanolamide (125 mg/day) decrease the pain & reduced inflammatory cytokines
Decreased dysmenorrhea pain in girls by reducing oxidative stress and inflammatory biomarkers following supplementation with oleoylethanolamide: A randomized controlled trial

2022: In humans with stroke, three days of oleoylethanolamide (300 to 600 mg/day) to the standard treatment “improves short-term inflammatory, [oxidative stress], lipid, and biochemical parameters”
The Effect of Oleoylethanolamide (OEA) Add-On Treatment on Inflammatory, Oxidative Stress, Lipid, and Biochemical Parameters in the Acute Ischemic Stroke Patients: Randomized Double-Blind Placebo-Controlled Study

2022: In obese patients with nonalcoholic fatty liver disease, 12 weeks of oleoylethanolamide (250 mg/day) had significant effect on weight, body mass index, waist-to-hip ratio & weight to height ratio
The effect of oleoylethanolamide supplementation on pyroptotic cell death in obese patients with nonalcoholic fatty liver disease: A double-blinded randomized controlled clinical trial

2021: In humans with non-alcoholic fatty liver disease, 12 weeks of a combination of caloric restriction & oleoylethanolamide had significant fat mass reduction & a remarkable increase in resting metabolic rate
Expression of NF-κB, IL-6, and IL-10 genes, body composition, and hepatic fibrosis in obese patients with NAFLD-Combined effects of oleoylethanolamide supplementation and calorie restriction: A triple-blind randomized controlled clinical trial

2021: In humans eating the Mediterranean diet for 8 weeks, the diet lowered their plasma levels of anandamide & increase their levels of PEA & oleoylethanolamide while increasing abundance of key gut microbiome players & improving insulin sensitivity & inflammation
Mediterranean diet consumption affects the endocannabinoid system in overweight and obese subjects: possible links with gut microbiome, insulin resistance and inflammation

2020: In obese humans with non-alcoholic fatty liver disease, 12 weeks of a combination of caloric restriction & oleoylethanolamide improved energy & carbohydrate intakes, glycemic parameters, appetite sensations & metabolic risk factors
Oleoylethanolamide supplementation in obese patients newly diagnosed with non-alcoholic fatty liver disease: Effects on metabolic parameters, anthropometric indices, and expression of PPAR-α, UCP1, and UCP2 genes

2019: In humans with obesity, eight weeks of oleoylethanolamide (250mg/day) decrease energy & carbohydrate intakes as well as increasing the levels of the Akkermansia muciniphila bacterium (involved in energy homeostasis & inhibition of inflammation)
Investigation the effect of oleoylethanolamide supplementation on the abundance of Akkermansia muciniphila bacterium and the dietary intakes in people with obesity: A randomized clinical trial

2018: In obese people, two months of oleoylethanolamide (250 mg/day) call significant reductions in weight, body mass index, waist circumference & fat percent as well as decreased hunger, desire to eat, cravings for sweet food & increased fullness via increases of the PPAR-α receptor
Oleoylethanolamide increases the expression of PPAR-Α and reduces appetite and body weight in obese people: A clinical trial

2018: In premenopausal people their cravings for sweet- rich foods were inversely associated with oleoylethanolamide while positively associated with progesterone while oleoylethanolamide, progesterone & disinhibition were linked to craving carbohydrates
Structural equation modeling of food craving across the menstrual cycle using behavioral, neuroendocrine, and metabolic factors

2018: In Native Americans of the southwest, their concentrations of oleoylethanolamide correlated with sleeping energy expenditure levels & respiratory quotient, anandamide with sleeping & resting energy expenditure & 2-AG with sleeping energy expenditure
Peripheral Endocannabinoids Associated With Energy Expenditure in Native Americans of Southwestern Heritage

2015: In morbidly obese people who had gastric bypass surgery, the surgery increased all measured endocannabinoid levels with inverse correlations between PEA & oleoylethanolamide levels with body mass index
Gastric bypass in morbid obese patients is associated with reduction in adipose tissue inflammation via N-oleoylethanolamide (OEA)-mediated pathways

2015: In humans, foods richer in oleic acid content increased the circulating levels of oleoylethanolamide resulting in a significant reduction of energy intake
Oleic acid content of a meal promotes oleoylethanolamide response and reduces subsequent energy intake in humans

2014: In obese people, oleoylethanolamide levels had a correlation with BMI while this was an inverse relationship for non-obese people with similar interactions for food-related brain activation in cortical areas associated with reward processing
Oleoylethanolamide and human neural responses to food stimuli in obesity

2014: In humans, eating peanuts high in oleic acid decreased total energy intake
Lower energy intake following consumption of Hi-oleic and regular peanuts compared with iso-energetic consumption of potato crisps

2014: In humans, foods rich in dietary fatty acids increased levels of oleoylethanolamide & alpha-linolenoyl ethanolamide (ALEA) with the oleoylethanolamide demonstrating an inverse association with percent body fat
Modulation of plasma N-acylethanolamine levels and physiological parameters by dietary fatty acid composition in humans

2008: In humans, oleoylethanolamide prevented the oxidation of lipids & caused antioxidant effects
Effect of acylethanolamides on lipid peroxidation and paraoxonase activity

Preclinical Research

2024: In a mouse model of kidney injury, oleoylethanolamide (an analog of anandamide) lowered inflammation & fibrosis (scarring) as well as protected the kidney via the PPAR nuclear receptors that control genetic transcription
Oleoylethanolamide attenuates acute-to-chronic kidney injury: in vivo and in vitro evidence of PPAR-α involvement

2023: On creating a dairy snack to reduce weight containing oleoylethanolamide (an analog of anandamide)
Development of a functional dairy snack containing oleoylethanolamide that reduces food intake in normal-weight and obese minipigs

2023: In a mouse model of neuronal degeneration, oleoylethanolamide (an analog of anandamide) lowered neuroinflammation & prevented massive inflows of white blood cells into the cerebellum via the PPAR nuclear receptors (regulators of genetic transcription)
Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration

2023: In a mouse model of obesity, oleoylethanolamide (an analog of anandamide) reduced systemic inflammation via the lowering of cellular inflammatory reactions & proinflammatory cytokine levels as well as suppressing the production of reactive oxygen species by immune cells
Effect of oleoylethanolamide on systemic inflammation in the development of alimentary induced obesity in mice

2023: In a mouse model of stress, oleoylethanolamide (an analog of anandamide) helped with their anxiety & depressive behaviors
Oleoylethanolamide restores stress-induced prepulse inhibition deficits and modulates inflammatory signaling in a sex-dependent manner

2023: In the brain, oleoylethanolamide (an analog to anandamide) reaches the brain nuclei via circulation & acts as a signal to stop eating
"To brain or not to brain": evaluating the possible direct effects of the satiety factor oleoylethanolamide in the central nervous system

2023: In a mouse model of cocaine use disorder, oleoylethanolamide (an analog of anandamide) did not alter their taste for blow but it did block the increase of dopamine D1 receptor genes in the striatum & hippocampus as well as D2 & CB1 in the striatum
Oleoylethanolamide attenuates cocaine-primed reinstatement and alters dopaminergic gene expression in the striatum

2023: In a mouse model of Alzheimer's disease, oleoylethanolamide (an analog of anandamide) increased the clearance of Aβ plaques & rescued cognitive impairments via the PPARα nuclear receptors that control genetic transcription
Oleoylethanolamide facilitates PPARa and TFEB signaling and attenuates Ab pathology in a mouse model of Alzheimer's disease

2023: In mice, dietary oleic acid helped to regulate food intake via intestinal oleoylethanolamide synthesis
Dietary oleic acid contributes to the regulation of food intake through the synthesis of intestinal oleoylethanolamide

2022: In mice, certain gut bacteria contributed to the production of oleoylethanolamide which activated TRPV1 levels which sent an exercise signal to the brain
A microbiome-dependent gut-brain pathway regulates motivation for exercise

2022: In mice with a disease of dysregulated lipid levels treated by fenofibrate (a common drug for the condition), they had strong changes in their liver levels of PEA & oleamide
Profound Modification of Fatty Acid Profile and Endocannabinoid-Related Mediators in PPARα Agonist Fenofibrate-Treated Mice

2022: The endocannabinoid-like molecule oleoylethanolamide appears to be the native binding ligand for hypoxia-inducible factors 3α (HIF-3α, a cellular transcription factor that helps a cell respond to low oxygen conditions)
Identification of oleoylethanolamide as an endogenous ligand for HIF-3α

2022: In adults rats exposed to alcohol as teens, oleoylethanolamide (an endocannabinoid-like molecule that alters genetic transcription) caused them to drink less via the CB1 receptor
Attenuation of oleoylethanolamide-induced reduction of alcohol consumption in adult rats exposed intermittently to alcohol during adolescence


2022: In mice being fed a high-fat diet, the onset of obesity suppressed histamine release & lowered the production of oleoylethanolamide (OEA). Giving them extra OEA helped reduce lipid accumulation, inflammation & liver scarring
Diet-Induced Obesity Disrupts Histamine-Dependent Oleoylethanolamide Signaling in the Mouse Liver


2022: In a mouse model of obesity, oleoylethanolamide (an analog of anandamide) prevented negative changes to the heart, lessened weight gain & improved blood glucose
Oleoylethanolamide mitigates cardiac metabolic alterations secondary to obesity induced by high-fat diet in C57/BL6J mice

2021: In rats fed an obesity-inducing diet, the endocannabinoid oleoylethanolamide protected their livers from oxidative stress

Oleoylethanolamide Reduces Hepatic Oxidative Stress and Endoplasmic Reticulum Stress in High-Fat Diet-Fed Rats

2021: In a mouse model of neurodegeneration, the endocannabinoid oleoylethanolamide protects brain cells & ameliorates behavioral problems

Oleoylethanolamide Delays the Dysfunction and Death of Purkinje Cells and Ameliorates Behavioral Defects in a Mouse Model of Cerebellar Neurodegeneration

2021: In rats on an obesity diet, PEA as well as oleylethanolamide (OEA – another endocannabinoid) functioned as anti-obesity nutritional interventions

Palmitoleoylethanolamide Is an Efficient Anti-Obesity Endogenous Compound: Comparison with Oleylethanolamide in Diet-Induced Obesity

2021: In the brain of a model organism, the injection of PEA or oleoylethanolamide mediated the brain levels of serotonin & acetylcholine

In vivo brain levels of acetylcholine and 5-hydroxytryptamine after oleoylethanolamide or palmitoylethanolamide administrations are mediated by PPARα engagement

2020: In hibernating brown bears, high oleoylethanolamide levels could favor lipolysis & fatty acid oxidation in peripheral tissues as well as a conservation of an anorexigenic signal & the maintenance of torpor
Specific shifts in the endocannabinoid system in hibernating brown bears

2020: In a mouse model of colitis, oleoylethanolamide improve their disease score & colon integrity with lowered levels of pro inflammatory cytokines
The anti-inflammatory and immune-modulatory effects of OEA limit DSS-induced colitis in mice

2020: In the mouth, anandamide & oleoylethanolamide (a lesser-known endocannabinoid) combine with poly-L-lysine synergistically to combat mouth bacteria

Comparative Evaluation of Combinatory Interaction between Endocannabinoid System Compounds and Poly-L-lysine against Streptococcus mutans Growth and Biofilm Formation

2020: In female rats, oleoylethanolamide (the anadamide analogue) helps with the frustration around binge eating caused by stress

Oleoylethanolamide decreases frustration stress-induced binge-like eating in female rats: a novel potential treatment for binge-eating disorder

2019: In an animal model, the mast cells regulate ketogenesis (“a crucial metabolic adaptation to prolonged periods of food scarcity”) in the liver via oleoylethanolamide & histamine
Mast Cell-Derived Histamine Regulates Liver Ketogenesis via Oleoylethanolamide Signaling

2019: In inflamed cells, oleamide, NADA & oleoylethanolamide inhibited their increase in permeability
Endocannabinoids and endocannabinoid-like compounds modulate hypoxia-induced permeability in CaCo-2 cells via CB1, TRPV1, and PPARα

2018: In obese mice, oleoylethanolamide enhanced GLP-1 signaling & worked with exendin-4 (Ex4) to promote weight loss, decrease eating & increase energy expenditure
Oleoylethanolamide modulates glucagon-like peptide-1 receptor agonist signaling and enhances exendin-4-mediated weight loss in obese mice

2018: In mice, oleoylethanolamide improve the gut microbiome & reduced intestinal cytokines from immune cells toward a "lean-like phenotype"
Oleoylethanolamide treatment affects gut microbiota composition and the expression of intestinal cytokines in Peyer's patches of mice

2018: In sebocytes, oleoylethanolamide promotes lipid synthesis – also present, GPR 119 receptors (recently de-orphanized as a receptor of OEA)

Endocannabinoid-like molecule oleoylethanolamide promotes sebaceous lipid synthesis

2017: In a rat model of alcohol use disorder, oleoylethanolamide before drinking lowered neuroinflammation & lessened depression during acute withdrawal
Oleoylethanolamide prevents neuroimmune HMGB1/TLR4/NF-kB danger signaling in rat frontal cortex and depressive-like behavior induced by ethanol binge administration

2016: In rat brains, the activation of CB1 receptors by anandamide increased signaling “gastrointestinal autonomic insula (GI-Au-I) and the gustatory insula (Gu-I) [124], regions of the brain that integrate taste information from taste buds in the tongue and gastrointestinal mechano-/chemo-sensory information, respectively, to create sensations of hunger or satiety “ while OEA attenuated that effect via GPR119
A role of CB1R in inducing θ-rhythm coordination between the gustatory and gastrointestinal insula

2016: In brown fat tissue, cold exposure or β3-adrenoceptor activation increased AEA & oleoylethanolamide levels
Endocannabinoid regulation in white and brown adipose tissue following thermogenic activation

2015: In a mouse model of chronic stress, oleoylethanolamide normalized sucrose preferences, reversed brain biomarker abnormalities (BDNF, MDA, SOD) in the hippocampus & prefrontal cortex, improved serum levels of ACTH, CORT & total antioxidant capacity, caused antidepressant effects & lowered hyperactivity of the HPA axis
Antidepressant-like effects of oleoylethanolamide in a mouse model of chronic unpredictable mild stress

2015: In roundworms, oleoylethanolamide extended their longevity via the LBP-8 & NHR-80 proteins & increased transcription of NHR-49 & NHR-80,
Aging. Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans

2014: In mice, oleoylethanolamide worked as well as rimonabant for decreased eating activity
Oleoylethanolamide: a novel potential pharmacological alternative to cannabinoid antagonists for the control of appetite

2014: In a rat model of Parkinson’s disease, OEA lowered neurotoxicity & protected the neurons via PPARα receptors
The systemic administration of oleoylethanolamide exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism

2014: In mice without histamine, the anorexic effects of oleoylethanolamide significantly attenuated
Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake

2013: In mice, oleoylethanolamide seemed to shift mice to less palatable yet healthier foods via dopamine
A gut lipid messenger links excess dietary fat to dopamine deficiency

2012: In insulin secreting β-cells, oleoylethanolamide protected the cells (not via GPR119) but this is blocked by FAAH inhibitors, so it might be the free oleate breakdown product
The cytoprotective effects of oleoylethanolamide in insulin-secreting cells do not require activation of GPR119

2011: In rats, oral sensation of fat intake lead to higher levels of NAPLE-PLD (which synthesizes oleoylethanolamide from NOPE) & a decrease in FAAH (which breaks down OEA) in the intestines via the vagus nerve & the CB1 receptor
Endocannabinoid signal in the gut controls dietary fat intake

2011: In mice on a high fat diet, five weeks of oleoylethanolamide & KDS-5104 (a nonhydrolyzable OEA analog) decreased body fat with lipid transport appearing to be a central explanation
Lipid transport function is the main target of oral oleoylethanolamide to reduce adiposity in high-fat-fed mice

2011: In rats, oleoylethanolamide made changes in the hypothalamus as well as in the gut peptides ghrelin & PYY
Oleoylethanolamide: effects on hypothalamic transmitters and gut peptides regulating food intake

2010: In rodents, brain (hypothalamus) injections of oleoylethanolamide lessen feeding via oxytocin release
The fat-induced satiety factor oleoylethanolamide suppresses feeding through central release of oxytocin

2009: In a rat model of memory, a FAAH inhibitor (URB597) increased levels of AEA, PEA & oleoylethanolamide as well as enhancing memory acquisition as did the PPAR-alpha agonist WY14643 as well
Fatty acid amide hydrolase (FAAH) inhibition enhances memory acquisition through activation of PPAR-alpha nuclear receptors

2009: In intestinal cells, oleoylethanolamide increased secretion of GLP-1 which was enhanced by a FAAH inhibitor (URB597) & enhanced insulin levels via the GRP119 receptor & was abolished by inhibition of protein kinase A
GPR119 is essential for oleoylethanolamide-induced glucagon-like peptide-1 secretion from the intestinal enteroendocrine L-cell

2008: In rats, oleoylethanolamide inhibited food intake by prolonging latency to feed & post meal interval proved by intriguing tests using adenoviral vector to cause overexpression
Targeted enhancement of oleoylethanolamide production in proximal small intestine induces across-meal satiety in rats

2008: In rat arteries, the ability of AEA to induce relaxation was potentiated by both PEA & oleoylethanolamide – the ability of PEA & oleoylethanolamide to cause relaxation may be via TRPV1

'Entourage' Effects of N-palmitoylethanolamide and N-oleoylethanolamide on Vasorelaxation to Anandamide Occur Through TRPV1 Receptors

2007: In rodent intestines, food deprivation decreased oleoylethanolamide levels while refeeding increase them as well as increased activity of the OEA-synthesizing enzyme NAPE-phospholipase D &decreased activity & expression of the OEA degrading enzyme FAAH
Food intake regulates oleoylethanolamide formation and degradation in the proximal small intestine

2006: After eating, Burmese pythons see a 300x increase in oleoylethanolamide levels
Postprandial increase of oleoylethanolamide mobilization in small intestine of the Burmese python (Python molurus)

2006: In rat fat tissue, cold exposure stimulated the synthesis of oleoylethanolamide via beta-receptors
Cold exposure stimulates synthesis of the bioactive lipid oleoylethanolamide in rat adipose tissue

2006: In rats, a variant of oleoylethanolamide resistant to breakdown cause increased feeding latency & meal intervals via the PPAR-alpha receptors
Pharmacological characterization of hydrolysis-resistant analogs of oleoylethanolamide with potent anorexiant properties

2005: In rats, oleoylethanolamide reduced foot intake without causing a conditioned taste aversion or reducing sodium appetite though it did cause changes in posture & reduced spontaneous activity
Mechanisms of oleoylethanolamide-induced changes in feeding behavior and motor activity

2005: In rat fat cells, oleoylethanolamide produce glucose intolerance without decreasing insulin levels (with no effects from PSA or oleic acid) partially mediated by the p38 & JNK kinases
Oleylethanolamide impairs glucose tolerance and inhibits insulin-stimulated glucose uptake in rat adipocytes through p38 and JNK MAPK pathways

2005: In rats, two weeks of oleoylethanolamide treatment decreased lipid content in liver cells as well as serum cholesterol & triglyceride levels
Oleoylethanolamide, an endogenous PPAR-alpha agonist, lowers body weight and hyperlipidemia in obese rats

2005: In mice, the anorexic effects of oleoylethanolamide though the vagus nerve is blocked by TRPV1 receptors
Oleoylethanolamide excites vagal sensory neurones, induces visceral pain and reduces short-term food intake in mice via capsaicin receptor TRPV1

2005: In mice, oleamide, PEA, FAAH inhibitors & oleoylethanolamide induced intestinal motility
Fatty acid amide hydrolase controls mouse intestinal motility in vivo

2004: In rat fat cells, oleoylethanolamide stimulated glycerol & fatty acid release well no effects on glucose uptake or oxidation while enhancing fatty acid oxidation in skeletal muscle, liver cells & heart cells via PPAR-alpha
Oleoylethanolamide stimulates lipolysis by activating the nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR-alpha)

2004: In rats, oleoylethanolamide “produces a profound and long-lasting inhibition of food intake in free-feeding rats” & an increase of OEA levels in the small intestine
Oleoylethanolamide inhibits food intake in free-feeding rats after oral administration

2003: In mice, first proof that oleoylethanolamide works via the PPAR-alpha receptor to regulate satiety & body weight by using PPAR-alpha knockouts
Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha

2001: In rats, food deprivation reduced the synthesis of oleoylethanolamide in the small intestine
An anorexic lipid mediator regulated by feeding

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