Peptide YY regulates bone remodeling in mice: a link between gut and skeletal biology.
OBJECTIVE
Gastrointestinal peptides are increasingly being linked to processes controlling the maintenance of bone mass. Peptide YY (PYY), a gut-derived satiety peptide of the neuropeptide Y family, is upregulated in some states that also display low bone mass. Importantly, PYY has high affinity for Y-receptors, particularly Y1R and Y2R, which are known to regulate bone mass. Anorexic conditions and bariatric surgery for obesity influence circulating levels of PYY and have a negative impact on bone mass, but the precise mechanism behind this is unclear. We thus examined whether alterations in PYY expression affect bone mass.


METHODS
Bone microstructure and cellular activity were analyzed in germline PYY knockout and conditional adult-onset PYY over-expressing mice at lumbar and femoral sites using histomorphometry and micro-computed tomography.


RESULTS
PYY displayed a negative relationship with osteoblast activity. Male and female PYY knockout mice showed enhanced osteoblast activity, with greater cancellous bone mass. Conversely, PYY over-expression lowered osteoblast activity in vivo, via a direct Y1 receptor mediated mechanism involving MAPK stimulation evident in vitro. In contrast to PYY knockout mice, PYY over expression also altered bone resorption, as indicated by greater osteoclast surface, despite the lack of Y-receptor expression in osteoclastic cells. While evident in both sexes, cellular changes were generally more pronounced in females.


CONCLUSIONS
These data demonstrate that the gut peptide PYY is critical for the control of bone remodeling. This regulatory axis from the intestine to bone has the potential to contribute to the marked bone loss observed in situations of extreme weight loss and higher circulating PYY levels, such as anorexia and bariatric obesity surgery, and may be important in the maintenance of bone mass in the general population.
Neuroscience Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
Iris P L
IP
Wong
Frank
F
Driessler
Ee Cheng
EC
Khor
Yan-Chuan
YC
Shi
Birgit
B
Hörmer
Amy D
AD
Nguyen
Ronaldo F
RF
Enriquez
John A
JA
Eisman
Amanda
A
Sainsbury
Herbert
H
Herzog
Paul A
PA
Baldock
D000818:Animals; D015519:Bone Density / Q000235:genetics; D016723:Bone Remodeling / Q000502:physiology*; D001862:Bone Resorption / Q000235:genetics; D001842:Bone and Bones / Q000502:physiology; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism; D015870:Gene Expression; D023061:Gene Order; D018390:Gene Targeting; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size / Q000235:genetics; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D019894:Peptide YY / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D019894:Peptide YY