Journal
INTEGRATIVE PHYSIOLOGY
Volume 1173, Issue S1, Pages E20-E30Publisher
BLACKWELL SCIENCE PUBL
DOI: 10.1111/j.1749-6632.2009.05061.x
Keywords
leptin; osteoblast; osteocalcin
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Funding
- NIDDK NIH HHS [R01 DK080756, K01 DK085194] Funding Source: Medline
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [K01DK085194, R01DK080756] Funding Source: NIH RePORTER
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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 beta 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.
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