Food intake is inhibited by oral oleoylethanolamide

Mie Julin Nielsen, Gitte Petersen, Arne Astrup, and Harald S. Hansen

Department of Pharmacology, Danish University of Pharmaceutical Sciences, Copenhagen 2100

Corresponding Author: hsh{at}dfh.dk

Oleoylethanolamide may be an endogenous regulator of food intake, and intraperitoneal injection of this compound decreases food intake in 24 h-starved rats (Rodriguez de Fonseca et al. 2001 Nature 414, 209-212). It is generally believed that this kind of lipid amides is rapidly catabolized in the gastrointestinal tract thereby preventing their use as oral anti-obesity compounds. We now show that oral oleoylethanolamide inhibits food intake dose-dependently 90 min after food presentation to starved rats. Food intake was reduced 15.5% (P < 0.01) by administration of 10 mg/kg of oleoylethanolamide. [3H]-Oleoylethanolamide was used to assess the degree of catabolism in the gastro-intestinal tract. The endogenous level of this acylethanolamide was increased 11 times in the intestinal tissue (i.e. 3.91 ± 0.98 nmol/g tissue, mean ± SEM) 90 min after food presentation as a result of the finding of 0.48% of the dose as intact oleoylethanolamide. These findings reveal unexpected properties of orally administered oleoylethanolamide, which may have the potential of a cheap and safe anti-obesity drug.

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