An investigation on the effects of OEA on feeding behaviour, activity and metabolic rate in mice

Annie Patel, Preeti Jethwa, Stephen Alexander, Francis Ebling. University of Nottingham, Nottingham, United Kingdom.

Fatty acid amide hydrolase is the primary hydrolysing enzyme for the majority of endogenous cannabinoids, including anandamide and N-oleoylethanolamide (OEA). It is expressed and active both centrally and peripherally. Endocannabinoids are synthesised de novo on demand and OEA is an endocannabinoid-like compound documented to accumulate in the small intestine and to increase upon feeding (Rodriguez de Fonseca et al., 2001). Furthermore, peripheral OEA administration has been shown to reduce both food intake and body weight gain in rats by activation of neurons in the wall of the small intestine, sending satiety signals via the vagal sensory neurone up to the satiety centre in the hypothalamus (Fu et al., 2003). The mechanisms of this action have not been fully characterised, as there is the possibility of various receptor involvement in the regulation of this response. Both transmitter-gated channels (TRPV1 vanilloid receptor) and nuclear receptors (peroxisome proliferator-activated receptor alpha, PPARα) have been implicated in the actions of OEA (Guzman et al., 2004; Wang et al., 2005), although other targets, including the orphan receptor GPR119 (Overton et al., 2006) are also possible. The aim of this investigation was to characterize the effects of OEA on food intake, locomotor activity and energy expenditure, helping to investigate the possible pathways of its actions in future studies.

Eight adult mice (male, C57bl, 25-30 g) were injected (10 μL/g) with either vehicle (5% Tween 80, 5% polyethelene glycol, 90% sterile saline) or OEA (1, 3 and 10 mg/kg) in a pseudo-random manner over four weeks, each animal acting as its own control. Metabolic parameters were measured using the OxyMax indirect calorimetry system. Preliminary results show administration of OEA to have a tendency, albeit non-significantly, to decrease food intake in a dose-dependent manner 0-1 h post injection. No hyperactivity or sedation was evident, nor was there any decrease in the number of meals. The decrease in food intake was associated with a decrease in oxygen consumption at 3 (P<0.01) and 10 mg/kg (P<0.05, 1-way ANOVA with post-hoc Bonferroni correction), however, no significant change in the respiratory quotient was observed.

In conclusion, OEA appears to decrease food intake and metabolic rate without causing any hyperactivity or sedation. Elucidation of the mechanism of action of OEA in this paradigm requires further investigation.

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Guzman, M, et al. (2004). J Biol Chem 279: 27849-27854.

Overton, HA, et al. (2006). Cell Metab 3: 167-175.

Rodríguez de Fonseca, F, et al. (2001). Nature 414: 209-212.

Wang, X, Miyares, RL, Ahern, GP (2005). J Physiol 564: 541-547.

We thank the MRC for a Studentship (AP) and the BBSRC for funding (PJ).