Peptide YY regulates bone turnover in rodents

Katherine E Wortley, Karen Garcia, Haruka Okamoto, Karen Thabet, Keith D Anderson, Victor Shen, Jim P Herman, David M Valenzuela, George D Yancopoulos, Matthias H Tschop, Andrew J Murphy, Mark W Sleeman

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Abstract

BACKGROUND AIMS: Peptide YY (PYY) and pancreatic polypeptide (PPY) are members of the neuropeptide Y peptide family. The neuropeptide Y receptor signaling pathway has been implicated in a number of physiologic processes, including the regulation of energy balance and bone mass. To investigate the contribution of endogenous PYY and PPY to these processes, we generated both Pyy- and Ppy-deficient mice. METHODS: Pyy(-/-) and Ppy(-/-) mice and their respective wild-type littermates were studied from 8 weeks to 9 months of age. Food intake, metabolic parameters, and locomotor activity were monitored using indirect calorimetry. Body composition and bone parameters were analyzed using dual energy x-ray absorptiometry, histomorphometry, and vertebral compression testing. RESULTS: Studies in these mice showed an osteopenic phenotype specific to the Pyy-deficient line, which included a reduction in trabecular bone mass and a functional deficit in bone strength. Furthermore, female Pyy(-/-) mice showed a greater sensitivity to ovariectomy-induced bone loss compared with wild-type littermates. No food intake or metabolic phenotype was apparent in male or female Pyy(-/-) mice on standard chow. However, female Pyy(-/-) mice on a high-fat diet showed a greater propensity to gain body weight and adiposity. No metabolic or osteopenic phenotype was observed in Ppy-deficient mice. CONCLUSIONS: These results indicate that endogenous PYY plays a critical role in regulating bone mass. In comparison, its role in regulating body weight is minor and is confined to situations of high-fat feeding.
Original languageEnglish
Pages (from-to)1534 - 1543
Number of pages10
JournalGastroenterology
Volume133
Issue number5
DOIs
Publication statusPublished - 2007

Cite this

Wortley, K. E., Garcia, K., Okamoto, H., Thabet, K., Anderson, K. D., Shen, V., Herman, J. P., Valenzuela, D. M., Yancopoulos, G. D., Tschop, M. H., Murphy, A. J., & Sleeman, M. W. (2007). Peptide YY regulates bone turnover in rodents. Gastroenterology, 133(5), 1534 - 1543. https://doi.org/10.1053/j.gastro.2007.08.024