Adiponectin regulates bone mass via opposite central and peripheral mechanisms through FoxO1.
Adiponectin regulates bone mass via opposite central and peripheral mechanisms through FoxO1.
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DOI：
10.1016/j.cmet.2013.04.009
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发表时间：
2013-06-04
期刊：
影响因子：
29
通讯作者：
Karsenty G
中科院分区：
文献类型：
--
作者：
Kajimura D;Lee HW;Riley KJ;Arteaga-Solis E;Ferron M;Zhou B;Clarke CJ;Hannun YA;DePinho RA;Guo XE;Mann JJ;Karsenty G
脂联素是一种脂肪因子，在正常饮食喂养的动物中具有不明确的功能，其合成可通过成骨细胞源性激素骨钙素增强。在这里，我们发现脂联素信号返回成骨细胞，阻碍其增殖和促进其凋亡，总的降低骨量和循环骨钙素水平。脂联素通过以PI 3激酶依赖性方式降低FoxO 1活性来实现这些功能，而不依赖于其已知的受体和信号通路。然而，随着时间的推移，这些局部效应被掩盖，因为脂联素在蓝斑神经元中也通过FoxO 1发出信号，以降低交感神经张力，从而增加骨量，并减少能量消耗。这项研究表明，脂联素具有不寻常的能力，以两种相反的方式调节相同的功能，这取决于它的作用部位，它部分地对抗瘦素对交感神经系统的影响。它还提出脂联素通过PI 3激酶-FoxO 1途径调节骨量。
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. Overtime 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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影响因子：
64.5
作者：
Ferron M;Wei J;Yoshizawa T;Del Fattore A;DePinho RA;Teti A;Ducy P;Karsenty G
通讯作者：
Karsenty G
影响因子：
18.2
作者：
通讯作者：
--
影响因子：
4.8
作者：
Henry, BA;Goding, JW;Clarke, IJ
通讯作者：
Clarke, IJ
DOI：
10.1073/pnas.0308744101
发表时间：
2004-03-02
影响因子：
11.1
作者：
Elefteriou, F;Takeda, S;Karsenty, G
通讯作者：
Karsenty, G
影响因子：
64.5
作者：
Lee, Na Kyung;Sowa, Hideaki;Karsenty, Gerard
通讯作者：
Karsenty, Gerard