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RESEARCH PRODUCT

Evidence for interactions between aroma compounds and the CB1 receptor: a way to regulate food intake?

subject

description

National audience; Obesity is a major cause of morbidity and mortality worldwide, characterised by a chronic imbalance of energy homeostasis. The regulation of dietary intake appears to be an effective way to regulate this imbalance. Furthermore, it is now well established that the endocannabinoid system influences appetite via the cannabinoid receptor type 1 (CB1): CB1 agonists can promote food intake while CB1 antagonists tend to decrease appetite (1). Interestingly, recent studies showed that CB1-like receptors are expressed in the olfactory epithelium of Xenopus laevis tadpoles (2). Elsewhere, it has been demonstrated that aroma perception is implicated in the process of satiety (3). Collectively, these studies suggest that aroma compounds could have an impact on food intake through interactions with the endocannabinoid system. We therefore aimed to explore this hypothesis by performing in silico and in vitro studies to identify aroma compounds able to interact with the CB1 receptor.In silico screening of around 3000 aroma compounds described in the Flavor-Base (Leffingwell and Assoc.) was performed using the agonist and antagonist pharmacophore models previously derived from literature data (4). In vitro studies were carried out in HEK293 cells expressing the mouse CB1 receptor. Interactions between candidate molecules and the CB1 receptor were measured using a functional assay (Glosensor assay, Promega). In addition, expression of CB1 mRNA in mouse tissues was assessed by quantitative real-time RT-PCR.From a set of aroma compounds predicted as candidates by the in silico study, three molecules were found to be moderate inverse agonists of the CB1 receptor. Furthermore, the CB1 receptor was significantly expressed in the olfactory bulb and olfactory mucosa of mice.On the basis of these findings, interactions between the endocannabinoid system and aroma compounds could be proposed as a mechanism involved in the establishment of satiety.