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Endocrine Abstracts (2013) 31 OC4.8 | DOI: 10.1530/endoabs.31.OC4.8

1Molecular Endocrinology Group, Imperial College, London, UK; 2Centre for Obesity research, University College London, London, UK; 3Queen Mary University of London, Oral Growth and Development, London, UK.


Bone loss in anorexia nervosa and following bariatric surgery is associated with an elevated circulating concentration of the gastrointestinal anorexigenic hormone peptide YY (PYY), which acts principally via the Y1R and Y2R receptors. Selective deletion of Y1R in osteoblasts or Y2R in the hypothalamus results in high bone mass, but deletion of PYY has resulted in conflicting skeletal phenotypes leading to uncertainty regarding its role in the regulation of bone mass. We hypothesised that PYY is a negative regulator of bone turnover and strength and determined the consequences of PYY deletion in knockout mice.

We investigated the skeletal phenotype of PYYKO mice during growth (postnatal day P14) and adulthood (P70 and P186) using X-ray microradiography, micro-CT, backscattered electron scanning electron microscopy (BSE-SEM), histology, histomorphometry and mechanical testing.

Long bones from adult PYYKO mice were stronger (maximum load: WT 9.59±5.3N, PYYKO 12.67±3.1N, P<0.001, n=7–8), more rigid (Stiffness: WT 28.98±1.65 N/mm, PYYKO 36.06±1.51 N/mm, P<0.01, n=7–8) and tougher (energy dissipated prior to fracture: WT 54.57±4.73%, PYYKO 82±4%, P<0.05, n=7–8;) than WT controls and displayed increased cortical thickness (WT 0.19±0.007 mm, PYYKO 0.22±0.004 mm, P<0.01, n=7–8) and mineral content (P<0.001, n=7–8). Investigation of the mechanisms responsible revealed the phenotype did not result from altered skeletal development or reduced osteoclastic bone resorption, thus suggesting enhanced osteoblastic bone formation as the underlying cause.

These data are consistent with a role for PYY as a negative regulator of bone formation that mediates the detrimental skeletal consequences of anorectic conditions such as starvation, malignancy and cardiac failure.

Declaration of funding

This work was supported by the Medical Research Council (grant numbers G800261) and a Royal College of Physicians of Ireland Travelling Fellowship in Endocrinology to M J B.

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