title: Novel role of Y1 receptors in the coordinated regulation of bone and energy homeostasis.
abstract: The importance of neuropeptide Y (NPY) and Y2 receptors in the regulation of bone and energy homeostasis has recently been demonstrated. However, the contributions of the other Y receptors are less clear. Here we show that Y1 receptors are expressed on osteoblastic cells. Moreover, bone and adipose tissue mass are elevated in Y1(-/-) mice with a generalized increase in bone formation on cortical and cancellous surfaces. Importantly, the inhibitory effects of NPY on bone marrow stromal cells in vitro are absent in cells derived from Y1(-/-) mice, indicating a direct action of NPY on bone cells via this Y receptor. Interestingly, in contrast to Y2 receptor or germ line Y1 receptor deletion, conditional deletion of hypothalamic Y1 receptors in adult mice did not alter bone homeostasis, food intake, or adiposity. Furthermore, deletion of both Y1 and Y2 receptors did not produce additive effects in bone or adiposity. Thus Y1 receptor pathways act powerfully to inhibit bone production and adiposity by nonhypothalamic pathways, with potentially direct effects on bone tissue through a single pathway with Y2 receptors.
authors.affiliation: Bone and Mineral Program, Garvan Institute of Medical Research, St Vincent's Hospital, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Baldock
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Allison
authors.forename: Pernilla
authors.initials: P
authors.lastname: Lundberg
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Lee
authors.forename: Katy
authors.initials: K
authors.lastname: Slack
authors.forename: En-Ju D
authors.initials: EJ
authors.lastname: Lin
authors.forename: Ronaldo F
authors.initials: RF
authors.lastname: Enriquez
authors.forename: Michelle M
authors.initials: MM
authors.lastname: McDonald
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: During
authors.forename: David G
authors.initials: DG
authors.lastname: Little
authors.forename: John A
authors.initials: JA
authors.lastname: Eisman
authors.forename: Edith M
authors.initials: EM
authors.lastname: Gardiner
authors.forename: Ernie
authors.initials: E
authors.lastname: Yulyaningsih
authors.forename: Shu
authors.initials: S
authors.lastname: Lin
authors.forename: Amanda
authors.initials: A
authors.lastname: Sainsbury
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
mesh_terms: D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015519:Bone Density / Q000502:physiology; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D007031:Hypothalamus / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D017476:Receptors, Neuropeptide Y / Q000235:genetics* / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor