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Endocrine regulation of energy metabolism by the skeleton.

The regulation of bone remodeling by an adipocyte-derived hormone implies that bone may exert a feedback control of energy homeostasis. To test this hypothesis we looked for genes expressed in osteoblasts, encoding signaling molecules and affecting energy metabolism. We show here that mice lacking the protein tyrosine phosphatase OST-PTP are hypoglycemic and are protected from obesity and glucose intolerance because of an increase in beta-cell proliferation, insulin secretion, and insulin sensitivity. In contrast, mice lacking the osteoblast-secreted molecule osteocalcin display decreased beta-cell proliferation, glucose intolerance, and insulin resistance. Removing one Osteocalcin allele from OST-PTP-deficient mice corrects their metabolic phenotype. Ex vivo, osteocalcin can stimulate CyclinD1 and Insulin expression in beta-cells and Adiponectin, an insulin-sensitizing adipokine, in adipocytes; in vivo osteocalcin can improve glucose tolerance. By revealing that the skeleton exerts an endocrine regulation of sugar homeostasis this study expands the biological importance of this organ and our understanding of energy metabolism.

Pubmed ID: 17693256

Authors

  • Lee NK
  • Sowa H
  • Hinoi E
  • Ferron M
  • Ahn JD
  • Confavreux C
  • Dacquin R
  • Mee PJ
  • McKee MD
  • Jung DY
  • Zhang Z
  • Kim JK
  • Mauvais-Jarvis F
  • Ducy P
  • Karsenty G

Journal

Cell

Publication Data

August 10, 2007

Associated Grants

  • Agency: NIAMS NIH HHS, Id: R01 AR045548
  • Agency: NIAMS NIH HHS, Id: R01 AR045548-08
  • Agency: NIDDK NIH HHS, Id: R01 DK080756
  • Agency: NICHD NIH HHS, Id: R01 HD065439

Mesh Terms

  • Animals
  • Bone and Bones
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Energy Metabolism
  • Genes, Lethal
  • Glucose
  • Glucose Intolerance
  • Hypoglycemia
  • Insulin
  • Insulin Resistance
  • Insulin-Secreting Cells
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Animal
  • Obesity
  • Protein Tyrosine Phosphatases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3