Pyy-KO Mouse

Peptide YY (PYY), a 36-amino-acid peptide, belongs to a family of peptides including neuropeptide Y (NPY) and pancreatic polypeptide. It is mainly secreted from L-cells in the ileum and large intestine, and released into the circulation as PYY(1-36) and PYY(3-36), with the latter being the major form [5]. PYY is involved in multiple physiological functions. It plays a key role in appetite regulation, with exogenous PYY(3-36) reducing energy intake and body weight in humans and animals by inhibiting NPY neurons and activating pro-opiomelanocortin neurons via Y2 receptors in the hypothalamic arcuate nucleus [5]. It also affects pancreatic islet function, intestinal motility, secretion, absorption, and visceral sensitivity, and may be related to bone mass regulation [1,2,3,4].

In Pyy knockout (KO) mice, juvenile mice had longer bones with decreased bone mineral content, while adult mice showed increased bone mineral content, increased mineralisation in cortical and trabecular compartments, and stronger long bones. These changes resulted from increased trabecular and cortical bone formation, demonstrating that PYY acts as a negative regulator of osteoblastic bone formation, which may be related to bone loss in anorexia or after bariatric surgery [4].

In conclusion, PYY has diverse biological functions. Through the study of Pyy KO mouse models, its role in bone mass regulation has been revealed. Additionally, it has implications in other areas such as diabetes, obesity, irritable bowel syndrome, and cancer, as it is involved in appetite regulation, pancreatic islet function, and intestinal physiology [1,2,3,6]. These findings help to better understand the physiological and pathological roles of PYY, providing potential directions for related disease treatment.

References:

1. Guida, Claudia, Ramracheya, Reshma. 2020. PYY, a Therapeutic Option for Type 2 Diabetes? In Clinical medicine insights. Endocrinology and diabetes, 13, 1179551419892985. doi:10.1177/1179551419892985. https://pubmed.ncbi.nlm.nih.gov/32030069/

2. Lafferty, Ryan A, Flatt, Peter R, Irwin, Nigel. . Established and emerging roles peptide YY (PYY) and exploitation in obesity-diabetes. In Current opinion in endocrinology, diabetes, and obesity, 28, 253-261. doi:10.1097/MED.0000000000000612. https://pubmed.ncbi.nlm.nih.gov/33395088/

3. El-Salhy, Magdy, Hatlebakk, Jan Gunnar, Hausken, Trygve. 2019. Possible role of peptide YY (PYY) in the pathophysiology of irritable bowel syndrome (IBS). In Neuropeptides, 79, 101973. doi:10.1016/j.npep.2019.101973. https://pubmed.ncbi.nlm.nih.gov/31727345/

4. Leitch, Victoria D, Brassill, Mary Jane, Rahman, Sofia, Williams, Graham R, Bassett, J H Duncan. 2019. PYY is a negative regulator of bone mass and strength. In Bone, 127, 427-435. doi:10.1016/j.bone.2019.07.011. https://pubmed.ncbi.nlm.nih.gov/31306808/

5. Ueno, Hiroaki, Yamaguchi, Hideki, Mizuta, Masanari, Nakazato, Masamitsu. 2007. The role of PYY in feeding regulation. In Regulatory peptides, 145, 12-6. doi:. https://pubmed.ncbi.nlm.nih.gov/17920705/

6. Jing, Fangyan, Liu, Guanglong, Zhang, Renyi, Li, Shenglong, Bao, Ming. 2022. PYY modulates the tumorigenesis and progression of colorectal cancer unveiled by proteomics. In American journal of cancer research, 12, 5500-5515. doi:. https://pubmed.ncbi.nlm.nih.gov/36628274/