An osteoblast-dependent mechanism contributes to the leptin regulation of insulin secretion

Eiichi Hinoi, Nan Gao, Dae Young Jung, Vijay Yadav, Tatsuya Yoshizawa, Daisuke Kajimura, Martin G. Myers, Streamson C. Chua, Qin Wang, Jason K. Kim, Klaus H. Kaestner, Gerard Karsenty

Research output: Contribution to journalReview articlepeer-review

47 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)E20-E30
JournalAnnals of the New York Academy of Sciences
Issue numberSUPPL. 1
StatePublished - Sep 2009


  • leptin
  • osteoblast
  • osteocalcin

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • History and Philosophy of Science


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