Neuropeptide W

Neuropeptide W or preprotein L8 is a short human neuropeptide. Neuropeptide W acts as a ligand for two neuropeptide B/W receptors, NPBWR1 and NPBWR2, which are integrated in GPCRs family of alpha-helical transmembrane proteins.

Structure
There are two forms of neuropeptide W whose precursor is encoded by NPW gene.

The 23-amino-acid form (neuropeptide W-23) is the one that activates the receptors whereas the C-terminally extended form (neuropeptide W-30) is less effective. These isoforms were demonstrated in different species like rat, human, chicken, mouse and pig.

The name of neuropeptid W is due to the tryptophan residues located on both sides, the N- side and -C side, in its two mature forms.

Location
Neuropeptide W was first identified in porcine hypothalamus in 2002. In humans, it is highly confined in neurons of the substantia nigra and the spinal cord, and fewer expressed in neurons of the hippocampus, hypothalamus, amygdala, parietal cortex and cerebellum. It can also be found in some peripheral tissues such as trachea, stomach, liver, kidney prostate, uterus and ovary. It has to be said that tissue distribution information is still lacking. For the moment, Neuropeptide W location differences between studied species (rat, mouse, chicken, pig) are slight, even though quantities differ between the organs.

Neuropeptide W in CNS
Neuropeptide W in the Central Nervous System is surely implicated in feeding activity and energy metabolism, in the adrenal axis stress response, and the regulation of neuroendocrine functions like the hormone release from the pituitary gland, but it is not considered as an inhibitory or regulatory factor in it. Neuropeptide W may also be involved in autonomic regulation, pain sensation, emotions, anxiety and fear.

It seems that regulation of feeding behaviour and energy metabolism is the primary function of the neuropeptide W signaling system. On the one hand, Neuropeptide W regulates the endocrine signals aimed at anterior hypophysis. This stimulates both the need for water (thirst) and the need for food (hunger). On the other hand, it plays a compensatory role in energy metabolism.

Regarding the adrenal axis response to stress, it plays a relevant role as a messenger in brain networks that help the activation of HPA (hypothalamic–pituitary–adrenal axis), which will cause the response to stress.

An example of neuroendocrine functions is the regulation of the secretion of cortisol due to the activation or deactivation of neuropeptide B/W receptors.

Moreover, Neuropeptide W is found in an area that is connected with preauthonomic centers in the brainstem and spinal cord. Because of this location, there is a chance that it can affect some cardiovascular function.

Infusion of neuropeptide W has been shown to suppress the eating of food and body weight and increase heat production and body temperature, this verifies its works as an endogenous catabolic signaling molecule.

Neuropepdide W in peripheral tissues
Nevertheless, function and physiological role of peripheric neuropeptid W is not clearly known.