Npy6r, a member of the neuropeptide Y receptor family, is involved in multiple physiological functions. It is known to be associated with the regulation of energy homeostasis, and is expressed in neurons where it can participate in various signaling pathways [1].

In Npy6r-deficient (Npy6r(-/-)) mice, there are significant impacts on body composition. Young Npy6r(-/-) mice have reduced body weight, lean mass, and adiposity, while older and high-fat-fed Npy6r(-/-) mice show low lean mass with increased adiposity. This is likely due to impaired vasoactive intestinal peptide (VIP) signaling in the suprachiasmatic nucleus (SCN), as Npy6r is co-expressed in VIP neurons. Pancreatic polypeptide (PP)-initiated signaling through Npy6r in VIP neurons regulates the growth hormone axis and body composition, as peripheral administration of PP has different effects on WT and Npy6r(-/-) mice in terms of energy expenditure, food intake, hypothalamic Ghrh mRNA expression, and serum IGF-1 levels [1].

In conclusion, Npy6r plays a crucial role in regulating energy homeostasis and body composition, as demonstrated by gene knockout mouse models. Understanding its function provides insights into the mechanisms underlying metabolic regulation and potentially related metabolic diseases [1].