Energy homeostasis is the result of a balance between energy intake and expenditure, and the hypothalamus plays a key role in the regulation of these processes. The hypothalamic prolactin-releasing peptide (PrRP) is involved in food intake regulation and energy homeostasis, although only its lipidized analogs exert central anorexigenic effects after peripheral administration. The aim of the present study was to delineate the extent of the Fos expression as a marker of neuronal activation within the hypothalamic structures involved in food intake regulation after peripherally administered palmitoylated PrRP31 (palm-PrRP31) and to determine whether the anorexigenic effect of peripherally administered palm-PrRP31 influence the activity of hypocretin (HCRT) and oxytocin (OXY) neurons, i.e., the neuropeptides crucially involved in the regulation of energy homeostasis. The data confirmed an anorexigenic effect of palm-PrRP31 treatment (5mg/kg, s.c.) in mice. In the palm-PrRP31-treated animals, a significant increase in Fos expression was observed in the hypothalamic paraventricular (PVN), dorsomedial (DMN), and arcuate (Arc) nuclei and in the neurons of the nucleus of the solitary tract (NTS). Moreover, significant Fos expression was observed in the lateral hypothalamic area (LHA) HCRT neurons and PVN OXY neurons after palm-PrRP31 administration. The present findings may indicate that palm-PrRP31 may be involved in energy homeostasis via the activation of several hypothalamic structures. Fos activation of the hypothalamic OXY and HCRT neurons in the PVN and LHA emphasizes the importance of the areas mentioned in the central action of palm-PrRP31.

Department of Human and Clinical Pharmacology University of Veterinary Medicine Košice Slovak Republic

Institute of Organic Chemistry and Biochemistry AS CR Prague Czech Republic

Laboratory of Functional Neuromorphology Institute of Experimental Endocrinology SAS Bratislava Slovak Republic

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