Neuropeptide W: a key player in the homeostatic regulation of feeding and energy metabolism?

Neuropeptide W (NPW), recently isolated from porcine hypothalamus, has been identified as the endogenous ligand for both NPBWR1 (GPR7) and NPBWR2 (GPR8), which belong to the orphan G protein-coupled receptor family. NPW is thought to play an important role in the regulation of feeding and drinking behavior, and to be related to the stress response. NPW-containing neurons are localized in several regions of the brain, including the hypothalamus, hippocampus, limbic system, midbrain, and brain stem. Accumulated evidence suggests that hypothalamic neuropeptides, such as neuropeptide Y (NPY), orexin, melanin-concentrating hormone (MCH), and proopiomelanocortin (POMC), are involved in the regulation of feeding behavior and energy homeostasis via neuronal circuits in the hypothalamus. NPW also forms part of the feeding-regulating neuronal circuitry in conjunction with other feeding-regulating peptide-containing neurons within the hypothalamus. We summarize our current understanding of the distribution of NPW and of the neuronal interactions between NPW and the different feeding-regulating peptide-containing neurons. This review also discusses evidence for the dichotomous actions of NPW on energy balance and the potential mechanisms involved.