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N-Acylated ethanolamines (NAE) are naturally-occurring lipids that have diverse bioactivities. For example, arachidonoyl ethanolamide (AEA) is an endogenous cannabinoid neurotransmitter that evokes cellular responses by activating the cannabinoid receptors, central cannabinoid (CB1) and peripheral cannabinoid (CB2). The different types of NAE are derived from glycerophospho-linked precursors by the activity of glycerophosphodiesterase 1 (GDE1). Glycerophospho-N-oleoyl ethanolamine is the precursor of oleoyl ethanolamide (OEA). OEA is an endogenous, potent agonist for PPARα, exhibiting an EC50 value of 120 nM in a transactivation assay. Systemic administration of OEA suppresses food intake and reduces weight gain in rats (10 mg/kg intraperitoneally) and PPARα wild-type mice, but not in PPARα knockout mice., Like AEA, OEA is metabolized by fatty acid amide hydrolase (FAAH).
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