Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors
Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors
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DOI：
10.1016/j.cell.2018.10.025
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发表时间：
2018-12-13
期刊：
影响因子：
64.5
通讯作者：
Spiegelman, Bruce M.
中科院分区：
文献类型：
--
作者：
Kim, Hyeonwoo;Wrann, Christiane D.;Spiegelman, Bruce M.
蝴蝶素是由肌肉分泌的，随着运动的增加而增加，并调节身体活动的某些有利效果。特别是，蝴蝶素已被证明对脂肪组织、大脑和骨骼有有益的影响。然而，骨骼对运动的反应不太清楚，虹膜蛋白的受体也还没有确定。在这里，我们显示了虹膜蛋白与αV类整合素的蛋白质结合，生物物理研究确定了虹膜蛋白和αV/β5整合素之间的相互作用表面。化学抑制αV整合素阻断了骨细胞和脂肪细胞中虹膜蛋白的信号和功能。淫羊藿素增加了骨细胞的存活和硬化素的产生，硬化素是骨重塑的局部调节剂。基因消融FNDC5(或淫羊藿素)可完全阻断卵巢切除引起的骨细胞性骨溶解，防止骨丢失，支持淫羊藿素在骨骼重塑中的重要作用。虹膜蛋白受体的鉴定将极大地促进我们对虹膜蛋白在运动和人体健康中的作用的理解。
Irisin is secreted by muscle, increases with exercise, and mediates certain favorable effects of physical activity. In particular, irisin has been shown to have beneficial effects in adipose tissues, brain, and bone. However, the skeletal response to exercise is less clear, and the receptor for irisin has not been identified. Here we show that irisin binds to proteins of the alpha V class of integrins, and biophysical studies identify interacting surfaces between irisin and alpha V/beta 5 integrin. Chemical inhibition of the alpha V integrins blocks signaling and function by irisin in osteocytes and fat cells. Irisin increases both osteocytic survival and production of sclerostin, a local modulator of bone remodeling. Genetic ablation of FNDC5 (or irisin) completely blocks osteocytic osteolysis induced by ovariectomy, preventing bone loss and supporting an important role of irisin in skeletal remodeling. Identification of the irisin receptor should greatly facilitate our understanding of irisin's function in exercise and human health.