TY - JOUR
T1 - Adiponectin regulates bone mass via opposite central and peripheral mechanisms through foxo1
AU - Kajimura, Daisuke
AU - Lee, Ha Won
AU - Riley, Kyle J.
AU - Arteaga-Solis, Emilio
AU - Ferron, Mathieu
AU - Zhou, Bin
AU - Clarke, Christopher J.
AU - Hannun, Yusuf A.
AU - Depinho, Ronald A.
AU - Guo, Edward X.
AU - Mann, J. John
AU - Karsenty, Gerard
N1 - Funding Information:
The authors thank Dr. S. Thomas and Dr. K. Kobayashi for Dbh −/− mice and Dbh-Cre mice, respectively, and Dr. J. Wei for generous help. This work was supported by grant DK58883 from the National Institutes of Health (G.K.).
PY - 2013/6/4
Y1 - 2013/6/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cmet.2013.04.009
DO - 10.1016/j.cmet.2013.04.009
M3 - Article
C2 - 23684624
AN - SCOPUS:84878783089
SN - 1550-4131
VL - 17
SP - 901
EP - 915
JO - Cell Metabolism
JF - Cell Metabolism
IS - 6
ER -