Osteocalcin differentially regulates β cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice
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- Mathieu Ferron
- Departments of *Genetics and Development and
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- Eiichi Hinoi
- Departments of *Genetics and Development and
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- Gerard Karsenty
- Departments of *Genetics and Development and
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- Patricia Ducy
- Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032
書誌事項
- 公開日
- 2008-04
- DOI
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- 10.1073/pnas.0711119105
- 公開者
- Proceedings of the National Academy of Sciences
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説明
<jats:p> The osteoblast-specific secreted molecule osteocalcin behaves as a hormone regulating glucose metabolism and fat mass in two mutant mouse strains. Here, we ask two questions: is the action of osteocalcin on β cells and adipocytes elicited by the same concentrations of the molecule, and more importantly, does osteocalcin regulate energy metabolism in WT mice? Cell-based assays using isolated pancreatic islets, a β cell line, and primary adipocytes showed that picomolar amounts of osteocalcin are sufficient to regulate the expression of the insulin genes and β cell proliferation markers, whereas nanomolar amounts affect adiponectin and Pgc1α expression in white and brown adipocytes, respectively. <jats:italic>In vivo</jats:italic> the same difference exists in osteocalcin's ability to regulate glucose metabolism on the one hand and affect insulin sensitivity and fat mass on the other hand. Furthermore, we show that long-term treatment of WT mice with osteocalcin can significantly weaken the deleterious effect on body mass and glucose metabolism of gold thioglucose-induced hyperphagia and high-fat diet. These results establish in WT mice the importance of this novel molecular player in the regulation of glucose metabolism and fat mass and suggest that osteocalcin may be of value in the treatment of metabolic diseases. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 105 (13), 5266-5270, 2008-04
Proceedings of the National Academy of Sciences