Oleoylethanolamide in the gut-brain axis [Tesi di dottorato]

Oleoylethanolamide (OEA), a PPAR-α agonist, is a mediator of satiety. After peripheral administration, OEA induces Fos expression and activation in areas of the CNS involved in the control of feeding behavior and energy homeostasis, such as the nucleus of the solitary tract (NST) and in the area postrema (AP) in the brainstem, the hypothalamic paraventricular (PVN), supraoptic (SON) and ventral tuberomammillary (vTMN) nuclei. Moreover, it is known to increase the noradrenergic trasmission in the NST and AP, by increasing the expression of the dopamine-β-hydroxylase (DBH). Visceral ascending fibers were hypothesized to mediate such effects, but recent findings demonstrate that abdominal vagal afferents are not necessary for the anorectic effect of OEA. In fact, OEA is able to decrease food intake both in rats that underwent a subdiaphragmatic vagal deafferentation (SDA), a surgical procedure that eliminates all abdominal vagal afferents but spares about 50% of the vagal efferents, and in SHAM controls. Thus, the aim of the present work was to better elucidate the role of abdominal vagal afferents in mediating OEA's effects on the CNS. To meet this aim, we subjected rats to SDA surgery, using SHAM rats as control. By using immunohistochemistry, Fos and DBH expression patterns were investigated in the NST, in the AP, and in the hypothalamus after OEA administration (10 mg kg -1). Consistently with the behavioral results, OEA increases Fos expression in the NST and in the AP. Moreover, in these nuclei, SDA did not cause any alteration of DBH expression. In the hypothalamus, in line with the behavioral results, OEA is able to increase Fos expression in the PVN and the vTMN, even though in the latter does not reach statistical significance. Overall, our findings indicate that vagal afferents are not strictly necessary for the satiety effect of OEA at both behavioral and neurochemical levels.

diritti: info:eu-repo/semantics/openAccess
In relazione con info:eu-repo/semantics/altIdentifier/hdl/11573/1307548
Valutatori esterni: M.B. Passani
C. Cifani
Settore BIO/14 - - Farmacologia

Tesi di dottorato. | Lingua: Inglese. | Paese: | BID: TD20018824