Neuronal Cell Adhesion Molecule 1 Regulates Leptin Sensitivity and Bone Mass

Xin Yan, Natalia L. Kononenko, Annemarie Brüel, Jesper Skovhus Thomsen, Matthew Poy

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)329-336
Number of pages8
JournalCalcified Tissue International
Volume102
Issue number3
DOIs
StatePublished - Mar 1 2018
Externally publishedYes

Fingerprint

Neuronal Cell Adhesion Molecules
Leptin
Cell Adhesion
Bone and Bones
Thigh
Bone Density
Homeostasis
Neurons
Brain
Hypothalamus
Central Nervous System
Body Weight

Keywords

  • Bone mass
  • Cadm1/SynCAM1
  • Leptin signaling
  • Micro-CT
  • Neuronal function
  • Skeleton metabolism
  • VGLUT2 excitatory neurons

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

Cite this

Neuronal Cell Adhesion Molecule 1 Regulates Leptin Sensitivity and Bone Mass. / Yan, Xin; Kononenko, Natalia L.; Brüel, Annemarie; Thomsen, Jesper Skovhus; Poy, Matthew.

In: Calcified Tissue International, Vol. 102, No. 3, 01.03.2018, p. 329-336.

Research output: Contribution to journalArticle

Yan, Xin ; Kononenko, Natalia L. ; Brüel, Annemarie ; Thomsen, Jesper Skovhus ; Poy, Matthew. / Neuronal Cell Adhesion Molecule 1 Regulates Leptin Sensitivity and Bone Mass. In: Calcified Tissue International. 2018 ; Vol. 102, No. 3. pp. 329-336.
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