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Novel role of Y1 receptors in the coordinated regulation of bone and energy homeostasis

Baldock, Paul A.; Allison, Susan LU ; Lundberg, Pernilla; Lee, Nicola J.; Slack, Katy; Lin, En-Ju D.; Enriquez, Ronaldo F.; McDonald, Michelle M.; Zhang, Lei and During, Matthew J., et al. (2007) In Journal of Biological Chemistry 282(26). p.19092-19102
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... (More)
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. (Less)
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publication status
published
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Journal of Biological Chemistry
volume
282
issue
26
pages
19092 - 19102
publisher
ASBMB
external identifiers
  • wos:000247475300051
  • scopus:34547105098
ISSN
1083-351X
DOI
10.1074/jbc.M700644200
language
English
LU publication?
yes
id
b04e1814-836c-4909-8982-0dae3b04706e (old id 648840)
date added to LUP
2007-12-05 09:26:11
date last changed
2017-11-05 03:43:14
@article{b04e1814-836c-4909-8982-0dae3b04706e,
  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.},
  author       = {Baldock, Paul A. and Allison, Susan and Lundberg, Pernilla and Lee, Nicola J. and Slack, Katy and Lin, En-Ju D. and Enriquez, Ronaldo F. and McDonald, Michelle M. and Zhang, Lei and During, Matthew J. and Little, David G. and Eisman, John A. and Gardiner, Edith M. and Yulyaningsih, Ernie and Lin, Shu and Sainsbury, Amanda and Herzog, Herbert},
  issn         = {1083-351X},
  language     = {eng},
  number       = {26},
  pages        = {19092--19102},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Novel role of Y1 receptors in the coordinated regulation of bone and energy homeostasis},
  url          = {http://dx.doi.org/10.1074/jbc.M700644200},
  volume       = {282},
  year         = {2007},
}