1RON, 1QFA4852109648ENSG00000122585ENSMUSG00000029819P01303P57774NM_000905NM_023456NP_000896NP_075945Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems.

High concentrations of neuropeptide Y synthesis and action have been found in the hypothalamus and hippocampus, specifically in the arcuate nucleus (ARC) and dentate gyrus.

[16] The dentate gyrus is significantly involved in cell proliferation, a process modulated by various internal factors including neuropeptide Y.

[16] Similar to the dentate gyrus, NPY has been found to increase cellular proliferation and differentiation in the sub-ventricular zone by specifically activating Y1 receptors in the ERK1/2 pathway.

Additionally, NPY was found in neuronal fibers that pass through the sub-ventricular zone and extend to other brain areas.

Furthermore, in situ hybridization results from the study showed the highest cellular levels of NPY mRNA in the arcuate nucleus (ARC) of the hypothalamus.

[25][27] Furthermore, these studies unanimously demonstrate that the stimulation of NPYergic activity via the administration of certain NPY agonists increases food intake compared to baseline data in rats.

Radioimmunoassay data, following the injection of BIIE0246, shows a significant increase in NPY release compared to the control group.

[31] In most obesity cases the increased secretion of NPY is a central / hypothalamic resistance to energy excess hormone signals such as leptin, that can be a result of a variety of reasons in the CNS.

Meanwhile, obesity-induced insulin resistance and the mutation of the leptin receptor (ObRb) results in the abolition of inhibition of NPYergic activity and ultimately food intake via other negative feedback mechanisms to regulate them.

[36] NPY neurons have been shown to interact with dopaminergic reward and emotion pathways in the nucleus accumbens and amygdala, respectively.

[7] Previous studies have identified NPY's anxiolytic effects to a possible therapeutic drug target for alcoholism.

[36] Additionally, another similar study identified that NPY expression may be connected to behavioral regulation in relation to alcohol dependence.

[36] Two results suggest that NPY might protect against alcoholism: Neuropeptide Y is considered to be an anxiolytic endogenous peptide and its levels can be modulated by stress.

[44] Studies of mice and monkeys show that repeated stress—and a high-fat, high-sugar diet—stimulate the release of neuropeptide Y, causing fat to build up in the abdomen.

Researchers believe that by manipulating levels of NPY, they could eliminate fat from areas where it was not desired and accumulate at sites where it is needed.