Imperial College London
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ProfessorGrahamWilliams

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Clinical Professor of Endocrinology
 
 
 
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Contact

 

+44 (0)20 3313 1383graham.williams

 
 
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Location

 

10N5Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Leitch:2019:10.1016/j.bone.2019.07.011,
author = {Leitch, VD and Brassill, MJ and Rahman, S and Butterfield, NC and Ma, P and Logan, JG and Boyde, A and Evans, H and Croucher, PI and Batterham, RL and Williams, GR and Bassett, JHD},
doi = {10.1016/j.bone.2019.07.011},
journal = {Bone},
pages = {427--435},
title = {PYY is a negative regulator of bone mass and strength},
url = {http://dx.doi.org/10.1016/j.bone.2019.07.011},
volume = {127},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - ObjectiveBone loss in anorexia nervosa and following bariatric surgery is associated with an elevated circulating concentration of the gastrointestinal, anorexigenic hormone, peptide YY (PYY). Selective deletion of the PYY receptor Y1R in osteoblasts or Y2R in the hypothalamus results in high bone mass, but deletion of PYY in mice has resulted in conflicting skeletal phenotypes leading to uncertainty regarding its role in the regulation of bone mass. As PYY analogs are under development for treatment of obesity, we aimed to clarify the relationship between PYY and bone mass.MethodsThe skeletal phenotype of Pyy knockout (KO) mice was investigated during growth (postnatal day P14) and adulthood (P70 and P186) using X-ray microradiography, micro-CT, back-scattered electron scanning electron microscopy (BSE-SEM), histomorphometry and biomechanical testing.ResultsBones from juvenile and Pyy KO mice were longer (P<0.001), with decreased bone mineral content (P<0.001). Whereas, bones from adult Pyy KO mice had increased bone mineral content (P<0.05) with increased mineralisation of both cortical (P<0.001) and trabecular (P<0.001) compartments. Long bones from adult Pyy KO mice were stronger (maximum load P<0.001), with increased stiffness (P<0.01) and toughness (P<0.05) compared to wild-type (WT) control mice despite increased cortical vascularity and porosity (P<0.001). The increased bone mass and strength in Pyy KO mice resulted from increases in trabecular (P<0.01) and cortical bone formation (P<0.05).ConclusionsThese findings demonstrate that PYY acts as a negative regulator of osteoblastic bone formation, implicating increased PYY levels in the pathogenesis of bone loss during anorexia or following bariatric surgery.
AU  - Leitch,VD
AU  - Brassill,MJ
AU  - Rahman,S
AU  - Butterfield,NC
AU  - Ma,P
AU  - Logan,JG
AU  - Boyde,A
AU  - Evans,H
AU  - Croucher,PI
AU  - Batterham,RL
AU  - Williams,GR
AU  - Bassett,JHD
DO  - 10.1016/j.bone.2019.07.011
EP  - 435
PY  - 2019///
SN  - 8756-3282
SP  - 427
TI  - PYY is a negative regulator of bone mass and strength
T2  - Bone
UR  - http://dx.doi.org/10.1016/j.bone.2019.07.011
UR  - https://www.sciencedirect.com/science/article/pii/S8756328219302856?via%3Dihub
UR  - http://hdl.handle.net/10044/1/71977
VL  - 127
ER  -
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