An Osteoblast-dependent Mechanism Contributes to the Leptin Regulation of Insulin Secretion
Article first published online: 11 SEP 2009
© 2009 New York Academy of Sciences.
Annals of the New York Academy of Sciences
Volume 1173, S1 Integrative Physiology pages E20–E30, September 2009
How to Cite
Hinoi, E., Gao, N., Jung, D. Y., Yadav, V., Yoshizawa, T., Kajimura, D., Myers, Jr., M. G., Chua, Jr., S. C., Wang, Q., Kim, J. K., Kaestner, K. H. and Karsenty, G. (2009), An Osteoblast-dependent Mechanism Contributes to the Leptin Regulation of Insulin Secretion. Annals of the New York Academy of Sciences, 1173: E20–E30. doi: 10.1111/j.1749-6632.2009.05061.x
- Issue published online: 16 SEP 2009
- Article first published online: 11 SEP 2009
Vol. 1234, Issue 1, 174, Article first published online: 11 OCT 2011
Our work focuses on genetic and molecular mechanisms for the reciprocal regulation of bone and energy metabolism orchestrated by leptin and osteocalcin. In the context of this reciprocal regulation, the finding that leptin inhibits insulin secretion by β cells while osteocalcin favors it is surprising. In exploring the molecular bases of this paradox we found that leptin, as is the case for most of its functions, uses a neuronal relay to inhibit insulin secretion. Cell-specific gene-deletion experiments revealed that a component of this neuronal regulation is the sympathetic innervation to osteoblasts. Under the control of leptin the sympathetic tone favors expression in osteoblasts of Esp, which inhibits the metabolic activity of osteocalcin. We further identify ATF4 as a transcription factor that regulates Esp expression and thereby insulin secretion and sensitivity. Taken together these data illustrate the tight connections between bone remodeling and energy metabolism and add further credence to the notion that the osteoblast is a bona fide endocrine cell type.