Neuropeptide Y knockout mice reveal a central role of NPY in the coordination of bone mass to body weight.
Neuropeptide Y knockout mice reveal a central role of NPY in the coordination of bone mass to body weight.
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神经肽Y基因敲除小鼠揭示了NPY在骨骼质量与体重的协调中的中心作用。
DOI：
10.1371/journal.pone.0008415
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发表时间：
2009-12-22
期刊：
影响因子：
3.7
通讯作者：
Herzog H
中科院分区：
文献类型：
--
作者：
Baldock PA;Lee NJ;Driessler F;Lin S;Allison S;Stehrer B;Lin EJ;Zhang L;Enriquez RF;Wong IP;McDonald MM;During M;Pierroz DD;Slack K;Shi YC;Yulyaningsih E;Aljanova A;Little DG;Ferrari SL;Sainsbury A;Eisman JA;Herzog H
全身能量水平的变化与体重和骨量的变化密切相关。在这里，我们表明，下丘脑信号有助于调节骨量的方式一致的中央感知的能量状态。缺乏神经肽Y（NPY）的小鼠具有显著增加的骨量，这与增强的成骨细胞活性和骨成骨转录因子Runx 2和Osterix的表达升高有关，神经肽Y是一种众所周知的促食欲因子，其下丘脑表达在禁食时增加。相比之下，野生型和NPY敲除（NPY-/-）小鼠（其中NPY在下丘脑中特异性过表达（AAV-NPY+））显示出骨质量的显著降低，尽管发展成肥胖表型。AAV-NPY+诱导的骨量损失与已知模拟禁食的中枢作用的模型一致，其也显示下丘脑NPY水平增加。因此，这些数据表明，除了良好的表征对体重的反应，骨骼组织也响应于下丘脑独立于体重的营养状态的感知。此外，AAV NPY+给药导致的骨量减少并不能完全纠正NPY-/-小鼠的高骨量表型，这表明外周NPY也可能是骨量的重要调节因子。事实上，我们证明了NPY的表达，特别是在成骨细胞。总之，这些数据将NPY鉴定为骨稳态信号的关键整合剂;当下丘脑NPY表达水平低时，在肥胖期间增加骨量，并且当下丘脑NPY表达水平高时，在“饥饿”条件下减少骨形成以保存能量。
Changes in whole body energy levels are closely linked to alterations in body weight and bone mass. Here, we show that hypothalamic signals contribute to the regulation of bone mass in a manner consistent with the central perception of energy status. Mice lacking neuropeptide Y (NPY), a well-known orexigenic factor whose hypothalamic expression is increased in fasting, have significantly increased bone mass in association with enhanced osteoblast activity and elevated expression of bone osteogenic transcription factors, Runx2 and Osterix. In contrast, wild type and NPY knockout (NPY −/−) mice in which NPY is specifically over expressed in the hypothalamus (AAV-NPY+) show a significant reduction in bone mass despite developing an obese phenotype. The AAV-NPY+ induced loss of bone mass is consistent with models known to mimic the central effects of fasting, which also show increased hypothalamic NPY levels. Thus these data indicate that, in addition to well characterized responses to body mass, skeletal tissue also responds to the perception of nutritional status by the hypothalamus independently of body weight. In addition, the reduction in bone mass by AAV NPY+ administration does not completely correct the high bone mass phenotype of NPY −/− mice, indicating the possibility that peripheral NPY may also be an important regulator of bone mass. Indeed, we demonstrate the expression of NPY specifically in osteoblasts. In conclusion, these data identifies NPY as a critical integrator of bone homeostatic signals; increasing bone mass during times of obesity when hypothalamic NPY expression levels are low and reducing bone formation to conserve energy under ‘starving’ conditions, when hypothalamic NPY expression levels are high.
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影响因子：
6.2
作者：
Bouxsein, ML;Pierroz, DD;Ferrari, SL
通讯作者：
Ferrari, SL
影响因子：
6.2
作者：
Baldock, Paul A.;Allison, Susan;Herzog, Herbert
通讯作者：
Herzog, Herbert
影响因子：
6.2
作者：
Baldock, PA;Sainsbury, A;Gardiner, EM
通讯作者：
Gardiner, EM
影响因子：
6.2
作者：
Hildebrand, T;Laib, A;Rüegsegger, P
通讯作者：
Rüegsegger, P
影响因子：
4.1
作者：
Kellenberger, S;Muller, K;Bilbe, G
通讯作者：
Bilbe, G