Adiponectin regulates bone mass via opposite central and peripheral mechanisms through foxo1

Daisuke Kajimura, Ha Won Lee, Kyle J. Riley, Emilio Arteaga-Solis, Mathieu Ferron, Bin Zhou, Christopher J. Clarke, Yusuf A. Hannun, Ronald A. Depinho, Edward X. Guo, J. John Mann, Gerard Karsenty

Research output: Contribution to journalArticlepeer-review

183 Scopus citations

Abstract

The synthesis of adiponectin, an adipokine with ill-defined functions in animals fed a normal diet, is enhanced by the osteoblast-derived hormone osteocalcin. Here we show that adiponectin signals back in osteoblasts to hamper their proliferation and favor their apoptosis, altogether decreasing bone mass and circulating osteocalcin levels. Adiponectin fulfills these functions, independently of its known receptors and signaling pathways, by decreasing FoxO1 activity in a PI3-kinase-dependent manner. Over time, however, these local effects are masked because adiponectin signals in neurons of the locus coeruleus, also through FoxO1, to decrease the sympathetic tone, thereby increasing bone mass and decreasing energy expenditure. This study reveals that adiponectin has the unusual ability to regulate the same function in two opposite manners depending on where it acts and that it opposes, partially, leptin's influence on the sympathetic nervous system. It also proposes that adiponectin regulation of bone mass occurs through a PI3-kinase-FoxO1 pathway.

Original languageEnglish (US)
Pages (from-to)901-915
Number of pages15
JournalCell Metabolism
Volume17
Issue number6
DOIs
StatePublished - Jun 4 2013

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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