Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPARalpha
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.
Thoughts?Modulation of meal pattern in the rat by the anorexic lipid mediator oleoylethanolamide.
Oleoylethanolamide (OEA) is a structural analog of the endogenous cannabinoid anandamide, which does not activate cannabinoid receptors. The biosynthesis of OEA in rat small intestine is increased by feeding and reduced by fasting. Moreover, OEA decreases food intake in food-deprived rats via a mechanism that requires intact sensory fibers (Rodriguez de Fonseca, 2001). These results suggest that OEA may contribute to the peripheral regulation of feeding. In the present study, we have investigated the effects of systemic OEA administration (1-20 mg/kg, intraperitoneal) on meal pattern in free-feeding and food-deprived rats. In free-feeding animals, OEA delayed feeding onset in a dose-dependent manner, but had no effect on meal size or postmeal interval. In food-deprived animals, OEA both delayed feeding onset and reduced meal size. The selective effects of OEA in free-feeding rats are strikingly different from those of the serotonergic anorexiant d-fenfluramine (which delayed feeding and reduced meal size) and the intestinal peptide cholecystokinin (which reduced meal size). These results suggest that OEA may participate in the regulation of satiety and may provide a chemical scaffold for the design of novel appetite-suppressing medications.
It appears to play a pivotal role in actually sending the 'fed' signal along with some evidence of a PPAR-alpha-'Satiety' sensation connection. OEA is a naturally coccuring compound and should be DSHEA compliant, so why hasnt that much research been done on it?
Also I wonder why studies havent been done in humans with OEA? Maybe it doesnt work in humans? But since it is naturally occurring in our blood administering it in humans should cause the same increases in the expression of FAT and FATP1 should it not?
Maybe the dosage has to be ridiculously high?
Your thoughts Doc?