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, Jr., Qin Wang, Jason K. Kim, Klaus H. Kaestner, Gerard Karsenty

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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)
JournalAnnals of the New York Academy of Sciences
Volume1173
Issue numberSUPPL. 1
DOIs
StatePublished - Sep 2009

Fingerprint

Osteoblasts
Leptin
Osteocalcin
Insulin
Energy Metabolism
Bone
Endocrine Cells
Bone Remodeling
Gene Deletion
Insulin Resistance
Molecular Biology
Transcription Factors
Genes
Cells
Bone and Bones
Secretion
Energy
Metabolism
Experiments

Keywords

  • leptin
  • osteoblast
  • osteocalcin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

An osteoblast-dependent mechanism contributes to the leptin regulation of insulin secretion. / Hinoi, Eiichi; Gao, Nan; Jung, Dae Young; Yadav, Vijay; Yoshizawa, Tatsuya; Kajimura, Daisuke; Myers, Martin G.; Chua, Jr., Streamson C.; Wang, Qin; Kim, Jason K.; Kaestner, Klaus H.; Karsenty, Gerard.

In: Annals of the New York Academy of Sciences, Vol. 1173, No. SUPPL. 1, 09.2009.

Research output: Contribution to journalArticle

Hinoi, E, Gao, N, Jung, DY, Yadav, V, Yoshizawa, T, Kajimura, D, Myers, MG, Chua, Jr., SC, Wang, Q, Kim, JK, Kaestner, KH & Karsenty, G 2009, 'An osteoblast-dependent mechanism contributes to the leptin regulation of insulin secretion', Annals of the New York Academy of Sciences, vol. 1173, no. SUPPL. 1. https://doi.org/10.1111/j.1749-6632.2009.05061.x
Hinoi, Eiichi ; Gao, Nan ; Jung, Dae Young ; Yadav, Vijay ; Yoshizawa, Tatsuya ; Kajimura, Daisuke ; Myers, Martin G. ; Chua, Jr., Streamson C. ; Wang, Qin ; Kim, Jason K. ; Kaestner, Klaus H. ; Karsenty, Gerard. / An osteoblast-dependent mechanism contributes to the leptin regulation of insulin secretion. In: Annals of the New York Academy of Sciences. 2009 ; Vol. 1173, No. SUPPL. 1.
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