Neuropeptide Y

Neuropeptide 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. It is secreted alongside other neurotransmitters such as GABA and glutamate. 

In the autonomic system it is produced mainly by neurons of the sympathetic nervous system and serves as a strong vasoconstrictor and also causes growth of fat tissue. In the brain, it is produced in various locations including the hypothalamus, and is thought to have several functions, including: increasing food intake and storage of energy as fat, reducing anxiety and stress, reducing pain perception, affecting the circadian rhythm, reducing voluntary alcohol intake, lowering blood pressure, and controlling epileptic seizures.

Neuropeptide Y has been identified as being synthesized in GABAergic neurons and to act as a neurotransmitter during cellular communication. Neuropeptide Y is expressed in interneurons. NPY exerts most of its effects through Neuropeptide Y receptors, mainly Y1, Y2, Y4, and Y6. All receptors have been indicated as participants in post-synaptic transmission activity, but the Y2 receptor has also been found to be involved in pre-synaptic processing.

The receptor protein that NPY operates on is a G protein-coupled receptor in the rhodopsin like 7-transmembrane GPCR family. Five subtypes of the NPY receptor have been identified in mammals, four of which are functional in humans. Subtypes Y1 and Y5 have known roles in the stimulation of feeding while Y2 and Y4 seem to have roles in appetite inhibition (satiety). Some of these receptors are among the most highly conserved neuropeptide receptors^{[citation needed]}.

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. The arcuate nucleus has been found to have one of the highest concentrations of NPY. This allows NPY to regulate neuroendocrine release of various hypothalamic hormones such as luteinizing hormone. Neuropeptide Y1 receptors have been found in highest density in the dentate gyrus along with a variety of other brain areas.

NPY is able to modulate the mitochondrial network by affecting the expression of many genes involved in mitochondrial functions and dynamics. It has been found that in breast muscle, ATP production genes (uncoupling protein, UCP; nuclear factor erythroid 2 like 2, NFE2L2) and a dynamics gene (mitofusin 1, MFN1) were upregulated (P < 0.05) at a low dose of NPY, while a high dose decreased (P < 0.05) markers of mitochondrial dynamics (mitofusin 2, MFN2; OPA1 mitochondrial dynamin-like GTPase, OPA1) and increased (P < 0.05) genes involved in mitochondrial biogenesis (D-loop, peroxisome proliferator-activated receptor gamma, PPARG).

Neuropeptide Y has been indicated as playing an important role in neurogenesis in various parts of the brain. Two particular brain areas where NPY affects neurogenesis are the sub-ventricular zone and the dentate gyrus of the hippocampus. These areas are where cell growth and proliferation occur into adulthood.

The dentate gyrus is significantly involved in cell proliferation, a process modulated by various internal factors including neuropeptide Y. Reduction or elimination of NPY released by interneurons decreased cell growth in this brain area. NPY affects neurogenesis by interacting with ERK kinase signaling pathways. Additionally, NPY acting on and stimulating Y1 receptors present on progenitor cell membranes in order to increase cell proliferation.