Endocrine Regulation of Energy Metabolism by the Skeleton
- 作者：Na Kyung Lee ; Hideaki Sowa ; Eiichi Hinoi ; Mathieu Ferron ; Jong Deok Ahn ; Cyrille Confavreux ; Romain Dacquin ; Patrick J. Mee ; Marc D. McKee ; Dae Young Jung ; Zhiyou Zhang ; Jason K. Kim ; Franck Mauvais-J
- 关键词：DEVBIO ; PROTEINS
- 刊名：Cell
- 出版年：2007
- 期刊代码：50_00928674
- 类别：med
- 出版时间：10 August 2007
- 卷：130
- 期：3
- 页码：456-469
- 文件大小：2334 K
摘要
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 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.