Novel role of Y1 receptors in the coordinated regulation of bone and energy homeostasis.
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.
Baldock
Paul A
PA
Bone and Mineral Program, Garvan Institute of Medical Research, St Vincent's Hospital, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia.
Allison
Susan J
SJ
Lundberg
Pernilla
P
Lee
Nicola J
NJ
Slack
Katy
K
Lin
En-Ju D
EJ
Enriquez
Ronaldo F
RF
McDonald
Michelle M
MM
Zhang
Lei
L
During
Matthew J
MJ
Little
David G
DG
Eisman
John A
JA
Gardiner
Edith M
EM
Yulyaningsih
Ernie
E
Lin
Shu
S
Sainsbury
Amanda
A
Herzog
Herbert
H
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
D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor