Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Medical Oncology Department, Giuseppe Mazzini Hospital, Teramo, Italy.
J Cell Physiol. 2022 Jan;237(1):551-565. doi: 10.1002/jcp.30501. Epub 2021 Jul 5.
Lipocalin 2 (LCN2) is an adipokine that accomplishes several functions in diverse organs. However, its importance in muscle and physical exercise is currently unknown. We observed that following acute high-intensity exercise ("Gran Sasso d'Italia" vertical run), LCN2 serum levels were increased. The Wnt pathway antagonist, DKK1, was also increased after the run, positively correlating with LCN2, and the same was found for the cytokine Interleukin 6. We, therefore, investigated the involvement of LCN2 in muscle physiology employing an Lcn2 global knockout (Lcn2 ) mouse model. Lcn2 mice presented with smaller muscle fibres but normal muscle performance (grip strength metre) and muscle weight. At variance with wild type (WT) mice, the inflammatory cytokine Interleukin 6 was undetectable in Lcn2 mice at all ages. Intriguingly, Lcn2 mice did not lose gastrocnemius and quadriceps muscle mass and muscle performance following hindlimb suspension, while at variance with WT, they lose soleus muscle mass. In vitro, LCN2 treatment reduced the myogenic differentiation of C2C12 and primary mouse myoblasts and influenced their gene expression. Treating myoblasts with LCN2 reduced myogenesis, suggesting that LCN2 may negatively affect muscle physiology when upregulated following high-intensity exercise.
脂联素 2（LCN2）是一种脂肪细胞因子，在多种器官中发挥多种功能。然而，其在肌肉和体育锻炼中的重要性目前尚不清楚。我们观察到，在急性高强度运动（“意大利大萨索垂直跑”）后，LCN2 血清水平升高。Wnt 通路拮抗剂 DKK1 在跑步后也增加，与 LCN2 呈正相关，细胞因子白细胞介素 6 也是如此。因此，我们使用 Lcn2 全局敲除（Lcn2-/-）小鼠模型研究了 LCN2 在肌肉生理学中的作用。Lcn2-/-小鼠的肌纤维较小，但肌肉性能（握力计）和肌肉重量正常。与野生型（WT）小鼠不同，Lcn2-/-小鼠在所有年龄段均未检测到炎症细胞因子白细胞介素 6。有趣的是，与 WT 相比，Lcn2-/-小鼠在下肢悬吊后不会失去比目鱼肌和股四头肌的质量和肌肉性能，但它们会失去跖肌的质量。在体外，LCN2 处理可降低 C2C12 和原代小鼠成肌细胞的成肌分化，并影响其基因表达。用 LCN2 处理成肌细胞可减少成肌作用，表明 LCN2 在高强度运动后上调时可能对肌肉生理学产生负面影响。
