Oleoylethanolamide: The role of a bioactive lipid amide in modulating eating behaviour

Abstract

Fatty acid ethanolamides are lipid mediators that regulate a plethora of physiological functions. One such bioactive lipid mediator, oleoylethanolamide (OEA), is a potent agonist of the peroxisome proliferator-activated receptor-alpha (PPAR-α), which modulates increased expression of the fatty acid translocase CD36 that enables the regulation of feeding behaviour. Consumption of dietary fat rich in oleic acid activates taste receptors in the gut activating specific enzymes that lead to the formation of OEA. OEA further combines with PPAR-α to enable fat oxidation in the liver, resulting in enhanced energy production. Evidence suggests that sustained ingestion of a high-fat diet abolishes the anorexic signal of OEA. Additionally, malfunction of the enterocyte that transforms oleic acid produced during fat digestion into OEA might be responsible for reduced satiety and hyperphagia, resulting in overweight and obesity. Thus, OEA anorectic signalling may be an essential element of the physiology and metabolic system regulating dietary fat intake and obesity. The evidence reviewed in this article indicates that intake of oleic acid, and thereby the resulting OEA imparting anorexic properties, is dependent on CD36, PPAR-α, enterocyte fat sensory receptors, histamine, oxytocin and dopamine; leading to increased fat oxidation and enhanced energy expenditure to induce satiety and increase feeding latency; and that a disruption in any of these systems will cease/curb fat-induced satiety.

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

“…46 In contrast, OEA increases the latency to feed, and thus, mediates the hypophagic effects. 4,6 This finding illustrated that the injection of OEA in free-feeding mice or rats elevated the feeding latency with no effect on meal size, while a delay in the onset of feeding as well as a reduction in meal size was reported with OEA administration in food-deprived animals. 42 Overall, the best action of OEA, which increases the feeding latency, makes it a novel satietyenhancing product.…”

“…These events related to taste recognition are regulated by signalling pathways, which are activated through the binding of long‐chain fatty acids to CD36 . Numerous studies performed on both humans and rodents indicated that CD36, a scavenger receptor expressed in multiple cell types, plays a critical role in mitochondrial fatty acid oxidation in skeletal muscle, and CD36 functions in regulating mitochondrial fatty acid oxidation along with carnitine palmitoyltransferase‐1 (CPT1), a protein that is responsible for the translocation of fatty acids from the cytosol to the mitochondrial matrix, where fatty acid oxidation occurs . In addition, some studies conducted on CD36‐deficient mice have reported defective fatty acid uptake, and thus disorders in fatty acid metabolism .…”

“…6,59,60 In addition, some studies conducted on CD36-deficient mice have reported defective fatty acid uptake, and thus disorders in fatty acid metabolism. 6,59 Moreover, human studies demonstrated that polymorphisms in the CD36 gene are associated with the alterations in plasma lipid levels, due to the reduced response to the taste cognition of OA. The CD36 protein plays an important role in the entry of OA into enterocytes, where it is converted into OEA.…”

“…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. In this regard, special attention has recently been paid to fatty acid ethanolamides (FAEs) …”

“…Fatty acid ethanolamides are bioactive lipid mediators derived from saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) or polyunsaturated fatty acids (PUFAs) precursors . Arachidonoylethanolamide (AEA, anandamide), stearoylethanolamide (SEA), palmitoylethanolamide (PEA), linoleoylethanolamide (LEA), and oleoylethanolamide (OEA) are examples of FAEs . The biochemical structure of OEA is presented in Figure .…”