Novel Role of Y1 Receptors in the Coordinated Regulation of Bone and Energy Homeostasis
Access status:
Open Access
Type
ArticleAuthor/s
Baldock, PAAllison, SJ
Lundberg, P
Lee, NJ
Slack, S
Lin, EJD
Enriquez, RF
McDonald, MM
Zhang, L
During, MJ
Little, DG
Eisman, JA
Gardiner, EM
Yulyaningsih, E
Lin, S
Herzog, H
Sainsbury, Amanda
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 recep- tors are less clear. Here we show that Y1 receptors are expressed on osteoblastic cells. Moreover, ...
See moreThe 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 recep- tors 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, con- ditional deletion of hypothalamic Y1 receptors in adult mice did not alter bone homeostasis, food intake, or adiposity. Further- more, 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 non- hypothalamic pathways, with potentially direct effects on bone tissue through a single pathway with Y2 receptors.
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See moreThe 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 recep- tors 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, con- ditional deletion of hypothalamic Y1 receptors in adult mice did not alter bone homeostasis, food intake, or adiposity. Further- more, 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 non- hypothalamic pathways, with potentially direct effects on bone tissue through a single pathway with Y2 receptors.
See less
Date
2007-10-01Publisher
Journal of Biological ChemistryShare