Endocrine regulation of energy metabolism by the skeleton
Endocrine regulation of energy metabolism by the skeleton
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DOI：
10.1016/j.cell.2007.05.047
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发表时间：
2007-08-10
期刊：
影响因子：
64.5
通讯作者：
Karsenty, Gerard
中科院分区：
文献类型：
--
作者：
Lee, Na Kyung;Sowa, Hideaki;Karsenty, Gerard
由脂肪细胞衍生的激素调节骨重塑意味着骨可能对能量稳态施加反馈控制。为了验证这一假设，我们寻找成骨细胞中表达的基因，编码信号分子并影响能量代谢。我们在这里表明，缺乏蛋白酪氨酸磷酸酶OST-PTP的小鼠是低血糖的，并且由于β细胞增殖、胰岛素分泌和胰岛素敏感性的增加而免受肥胖和葡萄糖耐受不良的影响。相反，缺乏成骨细胞分泌分子骨钙素的小鼠显示出β细胞增殖减少、葡萄糖耐受不良和胰岛素抵抗。从OST-PTP缺陷小鼠中去除一个骨钙素等位基因可纠正其代谢表型。在体外，骨钙素可以刺激β细胞中的细胞周期蛋白D1和胰岛素的表达，以及脂肪细胞中的脂联素（一种胰岛素增敏脂肪因子）;在体内，骨钙素可以改善葡萄糖耐量。通过揭示骨骼对糖稳态的内分泌调节，这项研究扩展了这个器官的生物学重要性和我们对能量代谢的理解。
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.