FATTY ACID AMIDE (OEA) INVOLVED IN DOPAMINE REGULATION OF FEEDING BEHAVIORS

Until recently fats were considered mere sources of energy and as components of biological membranes. However, research over the past 10-15 years has demonstrated a widely diverse array of biological activities associated with fatty acids and fatty acid derivatives as well as other lipid compounds. Bioactive lipids span the gamut of structural entities from simple saturated fatty acids to complex molecules such as those derived from various omega-3 and omega-6 fatty acids and those derived from sphingosine. All bioactive lipids exert their effects through binding to specific receptors, many of which are members of the G-protein coupled receptor (GPCR) family and also many of which have just recently been characterized. Bioactive lipids play important roles in energy homeostasis, cell proliferation, metabolic homeostasis, and regulation of inflammatory processes.

Oleoylethanolamide (OEA) is very important and potent member of the bioactive lipid family. This molecule is a member of the fatty-acid ethanolamide family that includes palmitoylethanolamide (PEA) and N-arachidonoylethanolamide (anandamide). Anandamide was identified as an endogenous ligand (endocannabinoid) for the cannabinoid receptors.

For more details on anandamide and other endocannabinoid functions go to the Endocannabinoids in Feeding Behavior and Energy Homeostasis page of my website.

OEA is produced by mucosal cells in the proximal small intestine from dietary oleic acid. Synthesis of OEA occurs on demand within the membrane of the cell. OEA has been shown to activate the fatty acid-sensing GPCR identified as GPR119 as well as the non-selective gated cation channel TRPV1 (transient receptor potential vanilloid 1), and to interact with intestinal fatty acid translocase (FAT/CD36) for uptake from the gut. Although the evidence is strong indicating that OEA may be the endogenous ligand for GPR119, its' interaction with FAT/CD36 is required for the satiety response elicited by this bioactive lipid. The demonstration that OEA is the most active endogenous ligand for GPR119 is of particular interest since previous work has demonstrated that OEA, when administered to laboratory animals, causes a significant reduction in food intake and body weight gain. These effects of OEA are the result of the activation of the nuclear receptor PPARα resulting in increased expression of fatty acid translocase and modification of feeding behavior and motor activity.

For more details on oleoylethanolamide (OEA) go to the Bioactive Lipids and Lipid Sensing Receptors page of my web site.

A recent paper just e-published in the journal Science demonstrates that OEA plays a critical role in the responses of the limbic system of the brain to the neurotransmitter, dopamine. Dopamine is known to exert a wide range of responses within the CNS and is of particular importance in the establishment of reward circuitry as relates to feeding behaviors and drug seeking behaviors.

A GUT LIPID MESSENGER LINKS EXCESS DIETARY FAT TO DOPAMINE DEFICIENCY

Several studies in humans and in laboratory animals have shown a link between obesity, particularly associated with a high-fat diet, and a decrease in dopamine release within the brain. This decrease in dopamine release is suspected to exacerbate obesity by provoking compensatory overfeeding as one way to restore reward sensitivity. Precisely how a high fat diet exerts a negative effect on CNS dopamine release is not yet fully understood. What is now known as a result of the finding in this recent Science paper is that administration of OEA to rodents is sufficient to re-establish the release of dopamine in response to a high-fat diet. The OEA (or vehicle control) in these experiments was administered intraduodenally and then the effects of feeding either low-fat or high-fat diets on dopamine release was examined. As a starting point, dopamine release was assayed in mice fed the high-fat diet or the low-fat diet. The high-fat diet mice failed to elicit the typical calorie-dependent dopamine release. In the low-fat diet fed animals consumption of a high calorie bolus of food elicited a strong dopamine release that was not affected either way by prior administration of OEA. On the other hand the high-fat diet fed animals showed a level of dopamine release that was similar to that of the low-fat diet fed animals ONLY after OEA administration. In addition, OEA administration was shown to produce an anorectic effect (lack of desire for food intake) in both low-fat and high-fat diet animals fed a bolus of high-calorie food. However, OEA produced these anorectic effects during oral low-fat intake in the low-fat diet fed animals while stimulating low-fat intake in the high-fat diet animals. Another consistent result from these experiments was that OEA administration resulted in decreased weight gain and a desire for fat intake in the high-fat diet fed mice.

The take home from this study is that there is great potential for the use of compounds, such as OEA, to re-establish the gut-lipid signaling pathways that beneficially regulate dopamine-mediated reward behaviors related to food intake and appetite. Of particular interest to human diets is the fact that extra-virgin olive oil has a high concentration of oleic acid which if the precursor to the gut synthesis of OEA. Another oil high in oleic acid, but not as readily available as a food-grade oil, is argan oil. Argan oil is better known for its use in cosmetics However, one can find this highly beneficial oil in food quality on the internet in bottled form as well as in gel cap form.

If you start spreading the word about the health benefits of argan oil I would appreciate you mentioning that you heard it from Dr. Michael W. King, and NOT Dr. Oz!!!