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Endocrine regulation of energy metabolism by the skeleton.

TitleEndocrine regulation of energy metabolism by the skeleton.
Publication TypeJournal Article
Year of Publication2007
AuthorsLee NKyung, Sowa H, Hinoi E, Ferron M, Ahn JDeok, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DYoung, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G
JournalCell
Volume130
Issue3
Pagination456-69
Date Published2007 Aug 10
ISSN0092-8674
KeywordsAnimals, 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
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.

DOI10.1016/j.cell.2007.05.047
Alternate JournalCell
PubMed ID17693256
PubMed Central IDPMC2013746
Grant ListR01 AR045548 / AR / NIAMS NIH HHS / United States
R01 AR045548-08 / AR / NIAMS NIH HHS / United States
R01 DK080756 / DK / NIDDK NIH HHS / United States
R01 HD065439 / HD / NICHD NIH HHS / United States
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