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Neuropeptide Y knockout mice reveal a central role of NPY in the coordination of bone mass to body weight

Baldock, Paul A.
Lee, Nicola J.
Driessler, Frank
Lin, Shu
Allison, Susan
Stehrer, Bernhard
Lin, En-Ju D.
Zhang, Lei
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Published in PloS one. 2009, vol. 4, no. 12, e8415
Abstract Changes in whole body energy levels are closely linked to alterations in body weight and bone mass. Here, we show that hypothalamic signals contribute to the regulation of bone mass in a manner consistent with the central perception of energy status. Mice lacking neuropeptide Y (NPY), a well-known orexigenic factor whose hypothalamic expression is increased in fasting, have significantly increased bone mass in association with enhanced osteoblast activity and elevated expression of bone osteogenic transcription factors, Runx2 and Osterix. In contrast, wild type and NPY knockout (NPY (-/-)) mice in which NPY is specifically over expressed in the hypothalamus (AAV-NPY+) show a significant reduction in bone mass despite developing an obese phenotype. The AAV-NPY+ induced loss of bone mass is consistent with models known to mimic the central effects of fasting, which also show increased hypothalamic NPY levels. Thus these data indicate that, in addition to well characterized responses to body mass, skeletal tissue also responds to the perception of nutritional status by the hypothalamus independently of body weight. In addition, the reduction in bone mass by AAV NPY+ administration does not completely correct the high bone mass phenotype of NPY (-/-) mice, indicating the possibility that peripheral NPY may also be an important regulator of bone mass. Indeed, we demonstrate the expression of NPY specifically in osteoblasts. In conclusion, these data identifies NPY as a critical integrator of bone homeostatic signals; increasing bone mass during times of obesity when hypothalamic NPY expression levels are low and reducing bone formation to conserve energy under 'starving' conditions, when hypothalamic NPY expression levels are high.
Keywords AdiposityAnimalsBody Weight/*physiologyBone and Bones/*anatomy & histology/cytology/metabolismFemaleHypothalamus/cytology/metabolismMaleMiceMice, KnockoutModels, BiologicalNeuropeptide Y/*deficiency/metabolismOrgan SizeOsteogenesisPhenotypeSignal Transduction
PMID: 20027231
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Research group Génétique des Ostéoporoses (544)
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BALDOCK, Paul A. et al. Neuropeptide Y knockout mice reveal a central role of NPY in the coordination of bone mass to body weight. In: PloS one, 2009, vol. 4, n° 12, p. e8415. doi: 10.1371/journal.pone.0008415 https://archive-ouverte.unige.ch/unige:19493

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Deposited on : 2012-04-23

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