TY - JOUR
T1 - Neuronal Cell Adhesion Molecule 1 Regulates Leptin Sensitivity and Bone Mass
AU - Yan, Xin
AU - Kononenko, Natalia L.
AU - Brüel, Annemarie
AU - Thomsen, Jesper Skovhus
AU - Poy, Matthew N.
N1 - Funding Information:
The authors are grateful for the excellent technical assistance of Jytte Utoft (Aarhus University). This work was funded by the Helmholtz Gemeinschaft, the Helmholtz Metabolic Dysfunction Consortium, and the European Foundation for the Study of Diabetes (EFSD, Germany), and the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD, Exc 229 to N.L.K.). The µCT scanner was kindly donated by the VELUX Foundation (Søborg, Denmark). The authors declare no competing interests.
Funding Information:
Acknowledgements The authors are grateful for the excellent technical assistance of Jytte Utoft (Aarhus University). This work was funded by the Helmholtz Gemeinschaft, the Helmholtz Metabolic Dysfunction Consortium, and the European Foundation for the Study of Diabetes (EFSD, Germany), and the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD, Exc 229 to N.L.K.). The µCT scanner was kindly donated by the VELUX Foundation (Søborg, Denmark).
Publisher Copyright:
© 2017, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - The central nervous system is widely known to exert control over our systemic physiology via several mechanisms including the regulation of skeletal metabolism. Neuronal circuits within the hypothalamus have been shown to impact bone mass via leptin-dependent and independent mechanisms; however, the full extent to which the brain controls bone homeostasis is not known. We previously identified cell adhesion molecule1 (Cadm1) as a regulator of body weight and energy homeostasis via its expression in multiple regions of the brain. Here, we show that loss of Cadm1 expression in excitatory neurons results in increased leptin sensitivity in addition to a concomitant reduction in bone mass. Femoral length, bone mineral content, diaphyseal cross-sectional area, and bone strength were all lower in Cadm1-deficient animals. Conversely, inducing expression of Cadm1 in excitatory neurons decreased leptin sensitivity and increased femoral length, bone mineral content, and diaphyseal cross-sectional area. Together, these results illustrate an essential role for this synaptic protein in the neuronal regulation of skeletal bone metabolism.
AB - The central nervous system is widely known to exert control over our systemic physiology via several mechanisms including the regulation of skeletal metabolism. Neuronal circuits within the hypothalamus have been shown to impact bone mass via leptin-dependent and independent mechanisms; however, the full extent to which the brain controls bone homeostasis is not known. We previously identified cell adhesion molecule1 (Cadm1) as a regulator of body weight and energy homeostasis via its expression in multiple regions of the brain. Here, we show that loss of Cadm1 expression in excitatory neurons results in increased leptin sensitivity in addition to a concomitant reduction in bone mass. Femoral length, bone mineral content, diaphyseal cross-sectional area, and bone strength were all lower in Cadm1-deficient animals. Conversely, inducing expression of Cadm1 in excitatory neurons decreased leptin sensitivity and increased femoral length, bone mineral content, and diaphyseal cross-sectional area. Together, these results illustrate an essential role for this synaptic protein in the neuronal regulation of skeletal bone metabolism.
KW - Bone mass
KW - Cadm1/SynCAM1
KW - Leptin signaling
KW - Micro-CT
KW - Neuronal function
KW - Skeleton metabolism
KW - VGLUT2 excitatory neurons
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U2 - 10.1007/s00223-017-0361-5
DO - 10.1007/s00223-017-0361-5
M3 - Article
C2 - 29134237
AN - SCOPUS:85033574052
SN - 0171-967X
VL - 102
SP - 329
EP - 336
JO - Calcified Tissue International
JF - Calcified Tissue International
IS - 3
ER -