title: 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.
authors: Department of Genetics & Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors: Na Kyung
authors: NK
authors: Lee
authors: Hideaki
authors: H
authors: Sowa
authors: Eiichi
authors: E
authors: Hinoi
authors: Mathieu
authors: M
authors: Ferron
authors: Jong Deok
authors: JD
authors: Ahn
authors: Cyrille
authors: C
authors: Confavreux
authors: Romain
authors: R
authors: Dacquin
authors: Patrick J
authors: PJ
authors: Mee
authors: Marc D
authors: MD
authors: McKee
authors: Dae Young
authors: DY
authors: Jung
authors: Zhiyou
authors: Z
authors: Zhang
authors: Jason K
authors: JK
authors: Kim
authors: Franck
authors: F
authors: Mauvais-Jarvis
authors: Patricia
authors: P
authors: Ducy
authors: Gerard
authors: G
authors: Karsenty
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004734:Energy Metabolism / Q000502:physiology*; D005804:Genes, Lethal; D005947:Glucose / Q000502:physiology*; D018149:Glucose Intolerance / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D007003:Hypoglycemia / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3
chemical_list: D007328:Insulin; D017027:Protein Tyrosine Phosphatases; C474713:Ptprv protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D005947:Glucose
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