比利时鲁汶大学Massimiliano Mazzone、Emanuele Berardi等研究人员合作发现，巨噬细胞来源的谷氨酰胺可促进卫星细胞和肌肉再生。该项研究成果于2020年10月28日在线发表在《自然》杂志上。
Title: Macrophage-derived glutamine boosts satellite cells and muscle regeneration
Author: Min Shang, Federica Cappellesso, Ricardo Amorim, Jens Serneels, Federico Virga, Guy Eelen, Stefania Carobbio, Melvin Y. Rincon, Pierre Maechler, Katrien De Bock, Ping-Chih Ho, Marco Sandri, Bart Ghesquire, Peter Carmeliet, Mario Di Matteo, Emanuele Berardi, Massimiliano Mazzone
Abstract: Muscle regeneration is sustained by infiltrating macrophages and the consequent activation of satellite cells1,2,3,4. Macrophages and satellite cells communicate in different ways1,2,3,4,5, but their metabolic interplay has not been investigated. Here we show, in a mouse model, that muscle injuries and ageing are characterized by intra-tissue restrictions of glutamine. Low levels of glutamine endow macrophages with the metabolic ability to secrete glutamine via enhanced glutamine synthetase (GS) activity, at the expense of glutamine oxidation mediated by glutamate dehydrogenase 1 (GLUD1). Glud1-knockout macrophages display constitutively high GS activity, which prevents glutamine shortages. The uptake of macrophage-derived glutamine by satellite cells through the glutamine transporter SLC1A5 activates mTOR and promotes the proliferation and differentiation of satellite cells. Consequently, macrophage-specific deletion or pharmacological inhibition of GLUD1 improves muscle regeneration and functional recovery in response to acute injury, ischaemia or ageing. Conversely, SLC1A5 blockade in satellite cells or GS inactivation in macrophages negatively affects satellite cell functions and muscle regeneration. These results highlight the metabolic crosstalk between satellite cells and macrophages, in which macrophage-derived glutamine sustains the functions of satellite cells. Thus, the targeting of GLUD1 may offer therapeutic opportunities for the regeneration of injured or aged muscles.