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Endocrine regulation of energy metabolism by the skeleton.

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.

SUBMITTER: Lee NK

PROVIDER: S-EPMC2013746 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature

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Endocrine regulation of energy metabolism by the skeleton.

Lee Na Kyung NK Sowa Hideaki H Hinoi Eiichi E Ferron Mathieu M Ahn Jong Deok JD Confavreux Cyrille C Dacquin Romain R Mee Patrick J PJ McKee Marc D MD Jung Dae Young DY Zhang Zhiyou Z Kim Jason K JK Mauvais-Jarvis Franck F Ducy Patricia P Karsenty Gerard G

Cell 20070801 3

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 sensit ...[more]

PMID: 17693256

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Endocrine regulation of energy metabolism by the skeleton.

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Endocrine regulation of energy metabolism by the skeleton.

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