Corticotrophin-releasing factor mediates vasoactive intestinal peptide-induced hypophagia and changes in plasma parameters

Abstract

Vasoactive intestinal peptide (VIP) and corticotrophin-releasing factor (CRF) are anorexigenic neuropeptides that act in the hypothalamus to regulate food intake. Intracerebroventricular (ICV) microinjection of VIP promotes increased plasma adrenocorticotrophic hormone (ACTH) and corticosterone, indicating that VIP activates hypothalamic-pituitary-adrenal axis. The aim of this study was to evaluate the interaction between VIP and CRF, by verifying the effects of ICV administration of VIP on the activity of neurons and CRF mRNA expression in paraventricular nucleus of hypothalamus (PVN). In addition, it was evaluated the effects of pretreatment with CRF type 1 receptor (CRFR1) antagonist (Antalarmin, ANT) or CRF type 2 receptor (CRFR2) antagonist (Antisauvagine-30, AS30) on VIP-induced changes on food intake and plasma parameters of male rats. Compared to Saline group, VIP increased not only the number of Fos-related antigens (FRA)-immunoreactive neurons in the PVN but also CRF mRNA levels in this nucleus. Both ANT and AS30 treatment attenuated the inhibition of food intake promoted by VIP, ANT showing a more pronounced effect. Both antagonists also attenuated VIP-induced reduction and enhancement of free fatty acids and corticosterone plasma levels, respectively, and only AS30 was able to attenuate the hyperglycemia. These results suggest that CRF is an important mediador of VIP effects on energy balance, and CRFR1 and CRFR2 are involved in these responses.