Endocrine regulation of energy metabolism by the skeleton.
Journal: 2007/September - Cell
ISSN: 0092-8674
Abstract:
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.
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Cell 130(3): 456-469

Endocrine regulation of energy metabolism by the skeleton

+6 authors
Department of Genetics & Development, Columbia University, New York, NY 10032, USA
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
CHO-A Biotechnology Research Institute, CHO-A Pharm. Co., Seoul 143-701, Korea
Ecole Normale Supérieure de Lyon, UMR5161, Laboratoire d’Endocrinologie Moléculaire et Différenciation Hématopoïétique et Osseuse, 69364 Lyon, France
Centre for Stem Cell Research, University of Cambridge, Cambridge CB2 1TN, United Kingdom
Faculty of Dentistry, and Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada H3A 2B2
Department of Cellular & Molecular Physiology, Penn State Medical Center, Hershey, PA 17033
Department of Medicine, Northwestern University School of Medicine, Chicago, IL 60611, USA
*Contact: ude.aibmuloc@2712kg; Tel: (212) 305 4011; Fax: (212) 923 2090
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SUMMARY

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 protected from obesity and glucose intolerance because of an increase in β-cell proliferation, insulin secretion and insulin sensitivity. In contrast, mice lacking the osteoblast-secreted molecule osteocalcin display decreased β-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 β-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.

SUMMARY

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