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Critical interplay between neuropeptide Y and sex steroid pathways in bone and adipose tissue homeostasis.
- Source :
-
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] 2009 Feb; Vol. 24 (2), pp. 294-304. - Publication Year :
- 2009
-
Abstract
- Important and novel roles for neuropeptide Y (NPY) signaling in the control of bone homeostasis have recently been identified, with deletion of either the Y1 or Y2 receptors resulting in a generalized increase in bone formation. Whereas the Y2 receptor-mediated anabolic response is mediated by a hypothalamic relay, the Y1-mediated response is likely mediated by osteoblastic Y1 receptors. The presence of Y1 receptors on osteoblasts and various other peripheral tissues suggests that, in addition to neuronal input, circulating factors may also interact with the Y1-mediated pathways. The skeletal and adipose tissue (peripheral and marrow) responses to Y1 receptor deficiency were examined after (1) leptin deficiency, (2) gonadectomy, and (3) hypothalamic NPY overexpression. Bone formation was consistently increased in intact Y1(-/-) mice. However, the hypogonadism of gonadectomy or leptin deficiency blocked this anabolism in male Y1(-/-) mice, whereas females remained unchanged. The Y1-mediated bone anabolic pathway thus seems to be dependent on the presence of intact androgen signaling. Y1 deficiency also led to increased body weight and/or adiposity in all experimental models, with the exception of male ob/ob, showing a general adipogenic effect of Y1 deficiency that is not dependent on androgens. Interestingly, marrow adipocytes were regulated differently than general adipose depots in these models. Taken together, this interaction represents a novel mechanism for the integration of endocrine and neural signals initiated in the hypothalamus and provides further insight into the coordination of bone and energy homeostasis.
- Subjects :
- Adiposity
Animals
Blood Glucose metabolism
Body Weight
Bone Resorption metabolism
Female
Gene Deletion
Gonadal Steroid Hormones blood
Leptin deficiency
Male
Mice
Obesity metabolism
Osteogenesis
Receptors, Neuropeptide Y deficiency
Thinness metabolism
Weight Gain
Adipose Tissue metabolism
Bone and Bones metabolism
Gonadal Steroid Hormones metabolism
Homeostasis
Neuropeptide Y metabolism
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1523-4681
- Volume :
- 24
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
- Publication Type :
- Academic Journal
- Accession number :
- 18847327
- Full Text :
- https://doi.org/10.1359/jbmr.081013