Neuropeptide Y knockout mice reveal a central role of NPY in the coordination of bone mass to body weight
| Autor: | Susan J. Allison, Ernie Yulyaningsih, Bernhard Stehrer, Amanda Sainsbury, Yan C. Shi, En-Ju D. Lin, Aygul Aljanova, John A. Eisman, Shu Lin, Iris P. L. Wong, Lei Zhang, Paul A. Baldock, Matthew J. During, Frank Driessler, Herbert Herzog, Katy Slack, Michelle M. McDonald, Ronald F. Enriquez, David G. Little, Dominique D. Pierroz, Serge Ferrari, Nicola J. Lee |
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| Rok vydání: | 2009 |
| Předmět: |
Male
lcsh:Medicine Diabetes and Endocrinology/Bone and Mineral Metabolism Mice 0302 clinical medicine Osteogenesis Neuropeptide Y lcsh:Science Adiposity 2. Zero hunger Mice Knockout 0303 health sciences Multidisciplinary Osteoblast Organ Size Neuropeptide Y receptor humanities RUNX2 medicine.anatomical_structure Phenotype Hypothalamus Knockout mouse Female medicine.drug Signal Transduction Research Article medicine.medical_specialty Neuropeptide 030209 endocrinology & metabolism Biology Models Biological Bone and Bones 03 medical and health sciences Internal medicine Orexigenic Neuropeptide Y/*deficiency/metabolism mental disorders medicine Animals Molecular Biology Body Weight/*physiology 030304 developmental biology Physiology/Endocrinology lcsh:R Body Weight Hypothalamus/cytology/metabolism Endocrinology Bone and Bones/*anatomy & histology/cytology/metabolism ddc:618.97 lcsh:Q Homeostasis Neuroscience |
| Zdroj: | PLoS ONE PLoS ONE, Vol 4, Iss 12, p e8415 (2009) PLOS ONE, Vol. 4, No 12 (2009) P. e8415 |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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