Npy6r, a member of the neuropeptide Y receptor family, has a role in multiple biological functions. It is involved in controlling energy homeostasis, and pancreatic polypeptide (PP)-initiated signaling through Npy6r in vasoactive intestinal peptide (VIP) neurons in the suprachiasmatic nucleus (SCN) regulates the growth hormone axis and body composition [2]. In the context of tumors, Npy6r is poorly expressed in most tumors, and in uveal melanoma (UVM), its low expression is associated with a better prognosis. It is also related to features of the UVM immune microenvironment, and gene enrichment analyses suggest its involvement in tumor-related pathways [1].

In Npy6r-deficient (Npy6r(-/-)) mice, young ones have reduced body weight, lean mass, and adiposity, while older and high-fat-fed Npy6r(-/-) mice have low lean mass with increased adiposity. These mice also show reduced hypothalamic growth hormone releasing hormone (Ghrh) expression and serum insulin-like growth factor-1 (IGF-1) levels relative to wild-type (WT), likely due to impaired VIP signaling in the SCN where Npy6r is co-expressed in VIP neurons [2].

In conclusion, Npy6r is crucial for energy homeostasis regulation as shown by gene knockout mouse models. In the field of oncology, its expression pattern and associations in UVM suggest potential as a prognostic marker. The study of Npy6r using KO mouse models has provided valuable insights into its role in these biological processes and disease conditions.

References:

1. Mei, ShiMin, Li, Yue, Kang, Xueran. 2022. Prognostic and Functional Analysis of NPY6R in Uveal Melanoma Using Bioinformatics. In Disease markers, 2022, 4143447. doi:10.1155/2022/4143447. https://pubmed.ncbi.nlm.nih.gov/35432628/

2. Yulyaningsih, Ernie, Loh, Kim, Lin, Shu, Sainsbury, Amanda, Herzog, Herbert. . Pancreatic polypeptide controls energy homeostasis via Npy6r signaling in the suprachiasmatic nucleus in mice. In Cell metabolism, 19, 58-72. doi:10.1016/j.cmet.2013.11.019. https://pubmed.ncbi.nlm.nih.gov/24411939/