Endocrine Regulation of Energy Metabolism by the Skeleton

• Published in: Cell Vol. 130; no. 3; pp. 456 - 469
• Main Authors: Lee, Na Kyung, Sowa, Hideaki, Hinoi, Eiichi, Ferron, Mathieu, Ahn, Jong Deok, Confavreux, Cyrille, Dacquin, Romain, Mee, Patrick J., McKee, Marc D., Jung, Dae Young, Zhang, Zhiyou, Kim, Jason K., Mauvais-Jarvis, Franck, Ducy, Patricia, Karsenty, Gerard
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.08.2007
• Subjects: Animals; Bone and Bones - metabolism; Bone and Bones - physiology; Cell Proliferation; Cells, Cultured; Coculture Techniques; DEVBIO; Energy Metabolism - physiology; Genes, Lethal; Glucose - physiology; Glucose Intolerance - enzymology; Glucose Intolerance - genetics; Glucose Intolerance - prevention & control; Hypoglycemia - enzymology; Hypoglycemia - genetics; Hypoglycemia - prevention & control; Insulin - physiology; Insulin Resistance - genetics; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - enzymology; Insulin-Secreting Cells - metabolism; Mice; Mice, Knockout; Mice, Transgenic; Models, Animal; Obesity - genetics; Obesity - metabolism; Obesity - prevention & control; Protein Tyrosine Phosphatases - deficiency; Protein Tyrosine Phosphatases - genetics; Protein Tyrosine Phosphatases - physiology; PROTEINS; Receptor-Like Protein Tyrosine Phosphatases, Class 3; PROTEINS; DEVBIO
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2007.05.047

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.