Neuropeptide Y (NPY) is a neuropeptide abundantly expressed in the mammalian central and peripheral nervous systems. It is a pleiotropic molecule influencing diverse functions like cell proliferation, cardiovascular and metabolic function, pain, and neuronal excitability. In the central nervous system, it acts as a neuromodulator affecting various pathways from cellular to circuit levels. NPY has multiple receptor subtypes, each activating specific signaling pathways [1].

In NPY -/- female mice, white adipose tissue mass decreased as the thermogenic program was upregulated, highlighting NPY's role in fat metabolism regulation [2]. Sympathetic-specific deletion of NPY in mice led to metabolic and cardiovascular defects, including reduced insulin secretion, glucose tolerance, cold tolerance, pupil size, and elevated heart rate, indicating its importance in these physiological processes [3].

In conclusion, NPY is crucial for a wide range of biological functions such as fat metabolism and metabolic and cardiovascular regulation. Gene-knockout mouse models have been instrumental in revealing its role in these processes, providing insights into potential therapeutic targets for diseases related to these functions, like postmenopausal adiposity and metabolic and cardiovascular diseases.

References:

1. Cattaneo, Stefano, Verlengia, Gianluca, Marino, Pietro, Simonato, Michele, Bettegazzi, Barbara. 2021. NPY and Gene Therapy for Epilepsy: How, When,... and Y. In Frontiers in molecular neuroscience, 13, 608001. doi:10.3389/fnmol.2020.608001. https://pubmed.ncbi.nlm.nih.gov/33551745/

2. Park, Seongjoon, Nayantai, Erkhembayar, Komatsu, Toshimitsu, Mori, Ryoichi, Shimokawa, Isao. . NPY Deficiency Prevents Postmenopausal Adiposity by Augmenting Estradiol-Mediated Browning. In The journals of gerontology. Series A, Biological sciences and medical sciences, 75, 1042-1049. doi:10.1093/gerona/gly282. https://pubmed.ncbi.nlm.nih.gov/30561530/

3. Kumari, Raniki, Pascalau, Raluca, Wang, Hui, Tampakakis, Emmanouil, Kuruvilla, Rejji. 2023. Sympathetic NPY controls glucose homeostasis, cold tolerance, and cardiovascular functions in mice. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.07.24.550381. https://pubmed.ncbi.nlm.nih.gov/37546870/