Oleoylethanolamide (OEA)

1) Conditions Studied

Oleoylethanolamide has been studied for various conditions, including:

• Obesity and weight management
• Appetite control
• Inflammatory conditions
• Neuroprotective effects
• Pain management
• Mood disorders and anxiety

2) Efficacy in Treating Conditions

The effectiveness of oleoylethanolamide in treating these conditions varies:

• There is some evidence that it may help with weight loss by reducing appetite and increasing fat burning.
• Its anti-inflammatory properties may contribute to reducing inflammation in certain conditions.
• Neuroprotective and analgesic effects have been observed in preclinical studies, but more research in humans is needed.
• Its impact on mood disorders and anxiety is not well-established and requires further study.

3) Health Benefits

Health benefits associated with oleoylethanolamide include:

• Regulation of feeding and body weight
• Potential improvement in lipid metabolism
• Anti-inflammatory effects
• Potential neuroprotective effects

4) Downsides

Oleoylethanolamide is generally considered safe, but potential downsides might include:

• Unknown long-term effects due to the lack of extensive human studies
• Potential interactions with medications, particularly those related to weight loss and appetite control
• Side effects, although uncommon, may include gastrointestinal discomfort

5) Genetic Variations

Regarding genetic variations and their impact on the effects of oleoylethanolamide:

• Some genetic variations in fatty acid metabolism may influence how individuals respond to oleoylethanolamide.
• Specific genetic polymorphisms might affect the expression and function of receptors that OEA interacts with, such as PPAR-alpha.
• However, the research is still emerging, and there is no definitive conclusion about the benefits or harm of OEA for particular genetic variations.

Oleoylethanolamide (OEA) and Its Role in Appetite Suppression

Oleoylethanolamide (OEA) is a lipid that occurs naturally in the body, known for its involvement in appetite regulation and lipid metabolism. Unlike anandamide, OEA does not interact with cannabinoid receptors but targets the peroxisome-proliferator-activated receptor-alpha (PPAR-alpha), a key player in lipid metabolism.

Effects of OEA

• OEA administration to rats suppresses feeding behavior, alters hypothalamic monoamines, increases anorexigenic neuropeptides, and affects gut peptide levels.
• OEA promotes satiety and reduces weight gain in mice by activating PPAR-alpha. Its anorectic effects are absent in mice lacking PPAR-alpha.
• OEA induces satiety, promotes fat oxidation, aids weight loss, and provides analgesic effects through the activation of PPAR-alpha and TRPV1 receptors.
• In rats, peripheral administration of OEA delays the onset of feeding and reduces meal size under fasting conditions, highlighting its role in controlling fullness.

Implications for Treatment

• The study suggests a novel role for PPAR-alpha in behavior regulation and indicates the potential for treating eating disorders with OEA-like agents.
• OEA's ability to suppress appetite and affect lipid and glucose metabolism positions it as a promising compound for obesity and metabolic disease treatment.

Additional Findings

• OEA production in the small intestine decreases during food deprivation and increases with dietary fat absorption.
• OEA plays a role in the external regulation of appetite, likely through the activation of specific brain regions, and requires peripheral sensory fibers.

Conclusion

Research on OEA points towards its significant influence on feeding behavior and body weight regulation, mediated by central and peripheral mechanisms involving PPAR-alpha. It offers a potential pathway for developing new appetite-suppressing drugs and treatments for obesity and related metabolic conditions.

References:

1. Oleoylethanolamide: effects on hypothalamic transmitters and gut peptides regulating food intake
2. Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha
3. Biological functions and metabolism of oleoylethanolamide
4. Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in rat brain
5. Formation and inactivation of endogenous cannabinoid anandamide in central neurons
6. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides
7. Modulation of meal pattern in the rat by the anorexic lipid mediator oleoylethanolamide
8. GPR119 is essential for oleoylethanolamide-induced glucagon-like peptide-1 secretion from the intestinal enteroendocrine L-cell
9. Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents
10. The orphan receptor GPR55 is a novel cannabinoid receptor
11. Evidence for novel cannabinoid receptors
12. GPR55 as a new cannabinoid receptor: still a long way to prove it
13. The identification of peroxisome proliferator-activated receptor alpha-independent effects of oleoylethanolamide on intestinal transit in mice
14. Properties of rat liver N-acylethanolamine amidohydrolase
15. Distribution of anandamide amidohydrolase in rat tissues with special reference to small intestine
16. Suppression of food intake, body weight, and body fat by jejunal fatty acid infusions
17. Administration of URB597, oleoylethanolamide or palmitoylethanolamide increases waking and dopamine in rats
18. Influence of oxytocin on feeding behavior in the rat
19. Mechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats
20. Neuropeptide exocytosis involving synaptotagmin-4 and oxytocin in hypothalamic programming of body weight and energy balance
21. The oxytocin receptor system: structure, function, and regulation
22. The fat-induced satiety factor oleoylethanolamide suppresses feeding through central release of oxytocin
23. Coordinate regulation of the expression of the fatty acid transport protein and acyl-CoA synthetase genes by PPARalpha and PPARgamma activators
24. Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting and refeeding
25. An anorexic lipid mediator regulated by feeding
26. Role of cholecystokinin in appetite control and body weight regulation
27. The gut hormone peptide YY regulates appetite
28. Antidepressant-like effects of oleoylethanolamide in a mouse model of chronic unpredictable mild stress
29. Oleoylethanolamide enhances β-adrenergic-mediated thermogenesis and white-to-brown adipocyte phenotype in epididymal white adipose tissue in rat
30. betaAR signaling required for diet-induced thermogenesis and obesity resistance
31. Effect of a beta-3 agonist on food intake in two strains of rats that differ in susceptibility to obesity
32. Beta3-adrenergic receptors stimulate glucose uptake in brown adipocytes by two mechanisms independently of glucose transporter 4 translocation
33. Insulin and the beta3-adrenoceptor differentially regulate uncoupling protein-1 expression
34. Metabolic and cellular plasticity in white adipose tissue II: role of peroxisome proliferator-activated receptor-alpha
35. PPARs in the Control of Uncoupling Proteins Gene Expression
36. Peroxisome proliferator-activated receptor α (PPARα) induces PPARγ coactivator 1α (PGC-1α) gene expression and contributes to thermogenic activation of brown fat: involvement of PRDM16
37. Administration of a dietary supplement ( N-oleyl-phosphatidylethanolamine and epigallocatechin-3-gallate formula) enhances compliance with diet in healthy overweight subjects: a randomized controlled trial
38. The effect of a dietary supplement (N-oleyl-phosphatidyl-ethanolamine and epigallocatechin gallate) on dietary compliance and body fat loss in adults who are overweight: a double-blind, randomized control trial
39. Agonists at GPR119 mediate secretion of GLP-1 from mouse enteroendocrine cells through glucose-independent pathways
40. Activation of GPR119 by fatty acid agonists augments insulin release from clonal β-cells and isolated pancreatic islets and improves glucose tolerance in mice
41. The cytoprotective effects of oleoylethanolamide in insulin-secreting cells do not require activation of GPR119
42. Oleoylethanolamide exerts partial and dose-dependent neuroprotection of substantia nigra dopamine neurons
43. Immunolocalization of peroxisome proliferator-activated receptors and retinoid X receptors in the adult rat CNS
44. Peroxisome proliferator-activated receptor-alpha activation as a mechanism of preventive neuroprotection induced by chronic fenofibrate treatment
45. Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human

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