Anandamide relative for weight loss?

[theobromos]

Oleylethanolamide is very closely related to the endogenous cannbinoid anandamide (arachidonylethanolamide) but its effects on appetite are not related to the cannabinoid receptors as it does not interact with them. I wonder if the displaced anandamide is responsible for the increase in appetite from cannabis use.

From the Nature website (there are some alphas missing):

Nature 425, 90 - 93 (04 September 2003); doi:10.1038/nature01921

Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-

JIN FU1, SILVANA GAETANI1, FARIBA OVEISI1, JESSE LO VERME1, ANTONIA SERRANO2, FERNANDO RODRÍGUEZ DE FONSECA2, ANJA ROSENGARTH3, HARTMUT LUECKE3, BARBARA DI GIACOMO4, GIORGIO TARZIA4 & DANIELE PIOMELLI1

1 Department of Pharmacology, University of California, Irvine, California 92697-4625, USA

2 Fundación Hospital Carlos Haya, Malaga, Spain

3 Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697-4625, USA

4 Institute of Medicinal Chemistry, University of Urbino, Italy

Correspondence and requests for materials should be addressed to D.P. ([email protected]).

Oleylethanolamide (OEA) is a naturally occurring lipid that regulates satiety and body weight. Although structurally related to the endogenous cannabinoid anandamide, OEA does not bind to cannabinoid receptors and its molecular targets have not been defined. Here we show that OEA binds with high affinity to the peroxisome-proliferator-activated receptor- (PPAR-), a nuclear receptor that regulates several aspects of lipid metabolism. Administration of OEA produces satiety and reduces body weight gain in wild-type mice, but not in mice deficient in PPAR-. Two distinct PPAR- agonists have similar effects that are also contingent on PPAR- expression, whereas potent and selective agonists for PPAR- and PPAR-/ are ineffective. In the small intestine of wild-type but not PPAR--null mice, OEA regulates the expression of several PPAR- target genes: it initiates the transcription of proteins involved in lipid metabolism and represses inducible nitric oxide synthase, an enzyme that may contribute to feeding stimulation. Our results, which show that OEA induces satiety by activating PPAR-, identify an unexpected role for this nuclear receptor in regulating behaviour, and raise possibilities for the treatment of eating disorders.