Leptin inhibits bone formation through a hypothalamic relay: A central control of bone mass
Leptin inhibits bone formation through a hypothalamic relay: A central control of bone mass
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DOI：
10.1016/s0092-8674(00)81558-5
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发表时间：
2000-01-21
期刊：
影响因子：
64.5
通讯作者：
Karsenty, G
中科院分区：
文献类型：
--
作者：
Ducy, P;Amling, M;Karsenty, G
性腺衰竭导致骨质流失，而肥胖阻止骨质流失，这增加了骨量、体重和性腺功能受共同途径调节的可能性。为了验证这一假设，我们研究了瘦素缺乏和瘦素受体缺乏的肥胖和性腺功能减退的小鼠。两种突变小鼠的骨形成增加，导致高骨量，尽管性腺功能减退和皮质醇增多。这种表型是显性的，不依赖于脂肪的存在，并且特异于瘦素信号传导的缺乏。在成骨细胞中没有瘦素信号传导，但脑室内输注瘦素导致瘦素缺陷和野生型小鼠的骨丢失。这项研究确定瘦素作为一种有效的抑制骨形成的作用，通过中枢神经系统，因此描述了中央性质的骨量控制及其障碍。
Gonadal failure induces bone loss while obesity prevents it. This raises the possibility that bone mass, body weight, and gonadal function are regulated by common pathways. To test this hypothesis, we studied leptin-deficient and leptin receptor-deficient mice that are obese and hypogonadic. Both mutant mice have an increased bone formation leading to high bone mass despite hypogonadism and hypercortisolism. This phenotype is dominant, independent of the presence of fat, and specific for the absence of leptin signaling. There is no leptin signaling in osteoblasts but intracerebroventricular infusion of leptin causes bone loss in leptin-deficient and wild-type mice. This study identifies leptin as a potent inhibitor of bone formation acting through the central nervous system and therefore describes the central nature of bone mass control and its disorders.