By activating PPAR-alpha receptors, oleoylethanolamide (OEA) acts as a gut-derived signal that regulates feeding behavior and metabolism. These effects are attracting a great attention, suggesting that OEA might be a potential target for novel therapies against obesity and eating disorders.
Preclinical and clinical observations suggest that the pharmacological effects of OEA on energy homeostasis are highly specific and mostly peripheral, although the involvement of central pathways was also demonstrated. These include noradrenergic, histaminergic and oxytocinergic systems of the brainstem and the hypothalamus that are involved in mediating OEA¿s effects on feeding behaviour. Whether these effects are directly induced by OEA permeating the brain parenchyma is still highly debated. Understanding this aspect is of importance to elucidate the pharmacological mode of action on this molecule and evaluate its potential benefits for the treatment of other pathologies often associated to obesity and eating disorders, such as neurodegenerative conditions and neuropsychiatric
pathologies, including anxiety and depression.
The aim of the present project is to elucidate whether OEA can permeate the brain from the circumventricular organs, and directly act at these sites modulating specific molecular targets.
Although obesity and eating disorders are major health problems worldwide, no efficacious and safe therapy is now available. Due to its effects on the regulation of metabolism and feeding behavior, OEA may be a pharmacological target to treat these diseases. Moreover, a large body of experimental evidence has been accumulating on the potential effects of OEA for the treatment of several other neuropathological/neuropsychiatric conditions, including neurodegenerative pathologies and depression. Hence, a deeper understanding of OEA's mechanism of action, especially at the CNS levels, may be the key to better characterize its possible impact for the development of new therapies in these fields.
Through this study, we expect to clearly understand whether peripherally administered OEA is, indeed, able to reach the CNS through the bloodstream and permeate the brain parenchyma in the circumventricular organs. We will shed light on this issue both by evaluating the fatty acid ethanolamides levels in the blood and in selected brain areas, and evaluating the changes of selected gene expression induced by OEA treatment. Since our analyses will be carried out on samples collected at different time points, the results of these experiments will help us to characterize the profile of both short- and long-term effect of OEA directly exerted in the CNS.
the results from this project will be a major advance for the scientific community, since the brain mechanisms involved in the effects mediated by OEA are still poorly understood. The theme of the research proposed is of high relevance, as obesity, eating disorders, neurodegenerative and depressive pathologies represent today a real and ever greater emergency to face.
Moreover, the results of this study could have a considerable potential clinical impact; the translational nature of this research is, indeed, supported by the availability of OEA as the only FDA- acknowledged supplement on the market under the name of RiduZone for the control of body-weight. This latter aspect would allow to test immediately the beneficial effects of OEA in human subjects. Overall, we expect that the successful completion of this project will generate a reliable pharmacological tool for the treatment of most prevalent pathological conditions in our society.