A systematic review of the effects of oleoylethanolamide, a high-affinity endogenous ligand of PPAR-α, on the management and prevention of obesity.

Along with an increase in overweight and obesity among all age groups, the development of efficacious and safe anti-obesity strategies for patients, as well as health systems, is critical. Oleoylethanolamide (OEA), a high-affinity endogenous ligand of nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR-α), plays important physiological and metabolic actions. OEA is derived from oleic acid, a monounsaturated fatty acid, which has beneficial effects on body composition and regional fat distribution. The role of OEA in the modulation of food consumption and weight management makes it an attractive molecule requiring further exploration in obesogenic environments. This systematic review was conducted to assess the effects of OEA on the obesity management, with emphasizing on its physiological roles and possible mechanisms of action in energy homeostasis. We searched PubMed/Medline, Google Scholar, ScienceDirect, Scopus, ProQuest, and EMBASE up until September 2019. Out of 712 records screened, 30 articles met the study criteria. The evidence reviewed here indicates that OEA, an endocannabinoid-like compound, leads to satiation or meal termination through PPAR-α activation and fatty acid translocase (FAT)/CD36. Additionally, the lipid-amide OEA stimulates fatty acid uptake, lipolysis, and beta-oxidation, and also promotes food intake control. OEA also exerts satiety-inducing effects by activating the hedonic dopamine pathways and increasing homeostatic oxytocin and brain histamine. In conclusion, OEA may be a key component of the physiological system involved in the regulation of dietary fat consumption and energy homeostasis; therefore, it is suggested as a possible therapeutic agent for the management of obesity.

Oleoylethanolamide Exhibits GPR119-Dependent Inhibition of Osteoclast Function and GPR119-Independent Promotion of Osteoclast Apoptosis.

Oleoylethanolamide (OEA), a bioactive lipid in bone, is known as an endogenous ligand for G protein-coupled receptor 119 (GPR119). Here, we explored the effects of OEA on osteoclast differentiation, function, and survival. While OEA inhibits osteoclast resorptive function by disrupting actin cytoskeleton, it does not affect receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. OEA attenuates osteoclast spreading, blocks actin ring formation, and eventually impairs bone resorption. Mechanistically, OEA inhibits Rac activation in response to macrophage colony-stimulating factor (M-CSF), but not RANKL. Furthermore, the OEA-mediated cytoskeletal disorganization is abrogated by GPR119 knockdown using small hairpin RNA (shRNA), indicating that GPR119 is pivotal for osteoclast cytoskeletal organization. In addition, OEA induces apoptosis in both control and GPR119 shRNAtransduced osteoclasts, suggesting that GPR119 is not required for osteoclast apoptosis. Collectively, our findings reveal that OEA has inhibitory effects on osteoclast function and survival of mature osteoclasts via GPR119-dependent and GPR119-independent pathways, respectively.

Plasma concentrations of oleoylethanolamide in a primary care sample of depressed patients are increased in those treated with selective serotonin reuptake inhibitor-type antidepressants.

Oleoylethanolamide (OEA) is a non-cannabinoid acylethanolamide with multiple physiological roles that has been proposed to have antidepressant-like activity in preclinical models. OEA shares biosynthetic pathways with anandamide (AEA) a transmitter involved in affective disorders and anxiety in humans. However, although the participation of OEA in depression has been proposed, both, the contribution of OEA to the depressive phenotype and the effect of antidepressant therapy on circulating levels of this and related non-cannabinoid acylethanolamides in humans are basically unknown. The main objective of this study is to compare the plasma concentrations of OEA and related acylethanolamides in a sample of primary care patients with depression (n = 69) with those of healthy non-depressed patients (n = 47). At the time of admission to the study, 22 patients were under selective serotonin reuptake inhibitor (SSRI) antidepressant treatment and 47 patients were not receiving any type of intervention. In addition, plasma concentrations of the endocannabinoid 2-AG and two related monoacylglycerols were monitored. Plasma OEA concentrations were found to be elevated in depressed patients and to correlate with somatic symptoms of depression. Plasma concentrations of both, AEA and 2-AG, were found to be elevated also in depressed patients. Further analysis demonstrated that the elevation observed in the plasma concentrations of both, OEA and 2-AG, was associated to SSRI antidepressant therapy at the time of recruitment. Further clinical research is needed to understand whether SSRI-induced elevations in OEA levels contribute to the response to SSRI in depressed patients as described in preclinical models.