Peptide YY regulates bone turnover in rodents.
OBJECTIVE
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.
Wortley
Katherine E
KE
Regeneron Pharmaceuticals Inc, Tarrytown, New York, USA.
Garcia
Karen
K
Okamoto
Haruka
H
Thabet
Karen
K
Anderson
Keith D
KD
Shen
Victor
V
Herman
Jim P
JP
Valenzuela
David
D
Yancopoulos
George D
GD
Tschöp
Matthias H
MH
Murphy
Andrew
A
Sleeman
Mark W
MW
D015502:Absorptiometry, Photon; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001823:Body Composition / Q000235:genetics / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000235:genetics / Q000502:physiology*; D001851:Bone Diseases, Metabolic / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001842:Bone and Bones / Q000378:metabolism*; D004041:Dietary Fats / Q000494:pharmacology; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010052:Ovariectomy; D019894:Peptide YY / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D013131:Spine / Q000473:pathology / Q000503:physiopathology
D004041:Dietary Fats; D019894:Peptide YY