title: Neuropeptide Y knockout mice reveal a central role of NPY in the coordination of bone mass to body weight.
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.
authors.affiliation: Osteoporosis and Bone Biology Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Baldock
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Lee
authors.forename: Frank
authors.initials: F
authors.lastname: Driessler
authors.forename: Shu
authors.initials: S
authors.lastname: Lin
authors.forename: Susan
authors.initials: S
authors.lastname: Allison
authors.forename: Bernhard
authors.initials: B
authors.lastname: Stehrer
authors.forename: En-Ju D
authors.initials: EJ
authors.lastname: Lin
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Enriquez
authors.forename: Iris P L
authors.initials: IP
authors.lastname: Wong
authors.forename: Michelle M
authors.initials: MM
authors.lastname: McDonald
authors.forename: Matthew
authors.initials: M
authors.lastname: During
authors.forename: Dominique D
authors.initials: DD
authors.lastname: Pierroz
authors.forename: Katy
authors.initials: K
authors.lastname: Slack
authors.forename: Yan C
authors.initials: YC
authors.lastname: Shi
authors.forename: Ernie
authors.initials: E
authors.lastname: Yulyaningsih
authors.forename: Aygul
authors.initials: A
authors.lastname: Aljanova
authors.forename: David G
authors.initials: DG
authors.lastname: Little
authors.forename: Serge L
authors.initials: SL
authors.lastname: Ferrari
authors.forename: Amanda
authors.initials: A
authors.lastname: Sainsbury
authors.forename: John A
authors.initials: JA
authors.lastname: Eisman
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
mesh_terms: D050154:Adiposity; D000818:Animals; D001835:Body Weight / Q000502:physiology*; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000166:cytology / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009478:Neuropeptide Y / Q000172:deficiency* / Q000378:metabolism; D009929:Organ Size; D010012:Osteogenesis; D010641:Phenotype; D015398:Signal Transduction
chemical_list: D009478:Neuropeptide Y