Feeding regulation in the brain: Involvement of Neuropeptide W

Abstract

Orphan G protein-coupled receptors (GPCRs) as targets to identify new transmitters have led over the last decade to the discovery of at least twelve novel neuropeptide families. Interestingly, several of these novel neuropeptides have physiological effects that include the modulation of food intake and energy expenditure. Neuropeptide W (NPW) is a novel neuropeptide which was recently isolated from the porcine hypothalamus and shown to be an endogenous ligand for the GPR7 and GPR8 orphan G protein-coupled receptors. NPW is widely distributed in the brain. Infusion of NPW is known to increase food intake in the light phase but inhibit intake in the dark phase. In spite of numerous morphological studies on NPW, its function has yet to be fully elucidated. Moreover, as the distribution of NPW-positive cell bodies in the hypothalamus has not been described, a detailed examination of NPW’s distribution and localization in this brain region is required. The expression of NPW mRNA was demonstrated in the hypothalamic paraventricular nucleus (PVN), arcuate nucleus (ARC), ventromedial nucleus (VMH) and lateral hypothalamus (LH). NPW-like immunoreactivity (LI) was dramatically enhanced in animals pretreated with colchicine. At the light microscopic level, NPW-LI cell bodies have been identified in the preoptic areas (POA), PVN, ARC, VMH, LH, periaqueductal gray (PAG), lateral parabrachial nucleus (LPB) and prepositus nucleus. NPW-LI axon terminals have also been observed in the POA, bed nucleus of the stria terminals, amygdala, PVN, ARC, VMH, LH by electron microscopy. In addition, at the electron microscopic level, NPW-LI cell bodies and dendritic processes were often observed receiving inputs from other unknown neurons in the ARC, PVN, VMH and amygdala. Moreover, double immunostaining experiments showed that NPW-LI axon terminals were in close apposition to orexin-, MCH-, and NPY-containing neurons in the hypothalamus. These morphological and physiological findings strongly suggest that NPW participates in the regulation of feeding behavior in harmony with other feeding-regulating neurons in the hypothalamus.