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

Article Article scientifique Article Neuropeptide Y knockout mice reveal a central role of NPY in the coordination of bone mass to body weight eng 2009 author Baldock Paul A. author Lee Nicola J. author Driessler Frank author Lin Shu author Allison Susan author Stehrer Bernhard author Lin En-Ju D. author Zhang Lei author Enriquez Ronald F. author Wong Iris P. L. author McDonald Michelle M. author During Matthew author Pierroz Dominique D. author Slack Katy author Shi Yan C. author Yulyaningsih Ernie author Aljanova Aygul author Little David G. author Ferrari Serge Livio 24314 author Sainsbury Amanda Jane 29058 author Eisman John Allan 24451 author Herzog Herbert e8415 10.1371/journal.pone.0008415 20027231 1932-6203 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794533/pdf/pone.0008415.pdf 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. Adiposity Animals Body Weight/*physiology Bone and Bones/*anatomy & histology/cytology/metabolism Female Hypothalamus/cytology/metabolism Male Mice Mice, Knockout Models, Biological Neuropeptide Y/*deficiency/metabolism Organ Size Osteogenesis Phenotype Signal Transduction Dewey 618.97 Dewey 616 56 Département de médecine 221 65 Département de réadaptation et gériatrie 22B false 289 Génétique des Ostéoporoses 544 PloS one 4 12 4bf56f52-ffec-4949-b7bd-fa8576365ce9 Article Public file1.pdf 660286 application/pdf CC BY openAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département de réadaptation et gériatrie

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Neuropeptide Y knockout mice reveal a central role of NPY in the coordination of bone mass to body weight	PloS one			2009	710	517

Archive ouverte UNIGE

Eisman, John Allan