NPY involvement in coupling food intake and ageing in teleost fishes

Neuropeptide Y (NPY), first isolated from pig brain [1], is a 36-amino acid peptide highly conserved among vertebrates. It acts through the binding to five different receptors (Y1, Y2, Y4, Y5, Y6) [2]. NPY is abundantly expressed in central and peripheral nervous system, as well as in other tissues, particularly in gastrointestinal tract. The extensive distribution in all vertebrate taxa suggests that this peptide plays important roles in many physiological functions. NPY is considered a strong orexigenic factor, binding to the Y1 receptor and activating signaling pathways in the hypothalamus of the mammalian brain [3]. In fish, NPY promotes food intake and affects the psychophysiological functions, i.e. decreasing swimming activity [4]. Furthermore, some studies suggest that the NPY system is also linked to the ageing process [5] as mediator of nutrient-sensing pathways. Here, we propose to expand our knowledge on the role of NPY during vertebrate ageing. To this aim, we compare, for the first time, the age-related central and peripheral expression of NPY in two teleost fishes, Nothobranchius furzeri (turquoise killifish) and Danio rerio (zebrafish), two consolidated model organisms with a different lifespan and feeding habits, although being both stomachless [6]. Experiments (Animal Welfare Body, University of Naples Federico II, PG/2018/0049615 - 22/05/2018) were performed on brain and gut of turquoise killifish, sampled at 5 and 27 weeks post-hatching, and zebrafish, sampled at 6 and 24 months post fertilization. In turquoise killifish, we confirmed an increase of NPY expression in the brain upon ageing [7] and the highest expression in the brain compared to gut, also in old specimens. We observed comparable data also in zebrafish, corroborating the idea that in these two species NPY has a main central regulation. Remarkably, the pattern confirmed a wider distribution of NPY along the whole brain, not only in the hypothalamic region but also in the epithelium lining the bulb and the anterior gut. By using two different fish species, serving both as models in aquaculture and in biomedical research, we provide new insights on the role of NPY in regulating food intake during vertebrate ageing.