瑞典卡洛琳卡学院Jorge L. Ruas团队发现，肌肉分泌的神经营养因子与肌纤维的氧化代谢和慢速运动神经元的身份相联系。该研究于2021年9月29日发表于国际一流学术期刊《细胞—代谢》杂志上。

研究人员表明，肌肉来源的神经营养因子（NRTN）作用于肌肉纤维和运动神经元（MN），使它们的特性耦合。使用肌肉特异性的NRTN转基因小鼠（HSA-NRTN）和MN体细胞的RNA测序，研究人员观察到逆行的NRTN信号传递促进了向慢速MN身份的转变。在肌肉中，NRTN增加了毛细血管密度和氧化能力，并诱发了有利于脂肪酸代谢而非糖酵解的转录重编程。这种对肌肉和MN的综合影响使HSA-NRTN小鼠变得瘦小，并具有出色的运动性能和运动协调性。

有趣的是，HSA-NRTN小鼠在很大程度上再现了其上游调节因子PGC-1ɑ1的肌肉特异性表达小鼠的表型。这项工作确定了NRTN是一种肌动素，它将肌肉的氧化能力与缓慢的MN特性联系起来。

据了解，耐力运动促进了骨骼肌的血管化、氧化代谢、纤维类型转换和神经肌肉接头的完整性。重要的是，肌肉纤维的代谢和收缩特性必须与支配MN的身份相联系。

附：英文原文

Title: Muscle-secreted neurturin couples myofiber oxidative metabolism and slow motor neuron identity

Author: Jorge C. Correia, Yildiz Kelahmetoglu, Paulo R. Jannig, Christoph Schweingruber, Dasha Shvaikovskaya, Liu Zhengye, Igor Cervenka, Naveen Khan, Michael Stec, Mariana Oliveira, Jik Nijssen, Vicente Martínez-Redondo, Serge Ducommun, Michele Azzolini, Johanna T. Lanner, Sandra Kleiner, Eva Hedlund, Jorge L. Ruas

Issue&Volume: 2021-09-29

Abstract: Endurance exercise promotes skeletal muscle vascularization, oxidative metabolism, fiber-type switching, and neuromuscular junction integrity. Importantly, the metabolic and contractile properties of the muscle fiber must be coupled to the identity of the innervating motor neuron (MN). Here, we show that muscle-derived neurturin (NRTN) acts on muscle fibers and MNs to couple their characteristics. Using a muscle-specific NRTN transgenic mouse (HSA-NRTN) and RNA sequencing of MN somas, we observed that retrograde NRTN signaling promotes a shift toward a slow MN identity. In muscle, NRTN increased capillary density and oxidative capacity and induced a transcriptional reprograming favoring fatty acid metabolism over glycolysis. This combination of effects on muscle and MNs makes HSA-NRTN mice lean with remarkable exercise performance and motor coordination. Interestingly, HSA-NRTN mice largely recapitulate the phenotype of mice with muscle-specific expression of its upstream regulator PGC-1ɑ1. This work identifies NRTN as a myokine that couples muscle oxidative capacity to slow MN identity.

DOI: 10.1016/j.cmet.2021.09.003

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00422-8