Lavi Gal, Horwitz Avital, Einstein Ofira, Zipori Reut, Gross Ofri, Birk Ruth
Department of Nutrition, Faculty of Health Sciences, Ariel University Israel.
Department of Physical Therapy, Faculty of Health Sciences, Ariel University Israel.
Am J Transl Res. 2022 Oct 15;14(10):7063-7079. eCollection 2022.
Irisin, a novel myokine that responds to exercise, was initially identified as a regulator of fat tissue metabolism. We aimed to investigate fibronectin type III domain-containing protein 5 (Fndc5)/irisin, auto/para-crine role in different muscle fibers, different activities, and muscle cell differentiation.
Using , , and muscle models, Fndc5 was studied at the physiological and molecular levels.
Following training, C57BL/6 mice (n=10) were subject to fast and slow-twitch muscles dissection and molecular analysis. Isolated mice (C57BL/6, n=14) slow and fast-twitch muscles were subject to electrical aerobic and anaerobic pulses stimulation (EPS). L6 muscle cells differentiation was characterized by Fndc5 differentiation-depended expression pattern parallel with significant hypertrophy, Myogenin elevation, and overlapping Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (Pgc-1α) expression pattern. Exogenous irisin significantly altered Fndc5 expression; augmented at early differentiation (3-4-fold, P<0.05) and decreased (2-fold, P<0.05) at late differentiation. Training induced a significant elevation in Fndc5/irisin and Pgc-1α expression levels in all muscle types compared to the sedentary state, where soleus muscle (slow) Fndc5 expression levels were significantly higher compared to levels in all other fast muscles (3-140-fold, P<0.001). Similarly, following EPS, Fndc5 expression levels were significantly augmented in the soleus slow muscle following both aerobic and anaerobic activity (3-3.5-fold, P<0.05) compared to extensor digitorum longus (fast) muscle.
Muscle cell's Fndc5 expression has a differentiation-depended pattern paralleling Pgc-1α expression and hypertrophy. Irisin autocrinally and significantly regulate Fndc5 and Pgc-1α in a differentiation-depended manner. Muscle Fndc5 expression levels are dependent on fiber type and activity type.
鸢尾素是一种对运动有反应的新型肌动蛋白，最初被鉴定为脂肪组织代谢的调节因子。我们旨在研究含III型纤连蛋白结构域蛋白5（Fndc5）/鸢尾素在不同肌纤维、不同活动及肌肉细胞分化中的自分泌/旁分泌作用。
使用 、 和 肌肉模型，在生理和分子水平上研究Fndc5。
训练后，对C57BL/6小鼠（n = 10）进行快、慢肌解剖和分子分析。对分离出的小鼠（C57BL/6，n = 14）慢、快肌进行有氧和无氧电脉冲刺激（EPS）。L6肌肉细胞分化的特征是Fndc5的表达模式依赖于分化，同时伴有显著的肥大、肌细胞生成素升高以及过氧化物酶体增殖物激活受体γ共激活因子1α（Pgc-1α）表达模式重叠。外源性鸢尾素显著改变Fndc5表达；在早期分化时增加（3 - 4倍，P < 0.05），在晚期分化时减少（2倍，P < 0.05）。与久坐状态相比，训练导致所有肌肉类型中Fndc5/鸢尾素和Pgc-1α表达水平显著升高，其中比目鱼肌（慢肌）的Fndc5表达水平显著高于所有其他快肌（3 - 140倍，P < 0.001）。同样，在EPS后，与趾长伸肌（快肌）相比，比目鱼慢肌在有氧和无氧活动后Fndc5表达水平均显著增加（3 - 3.5倍，P < 0.05）。
肌肉细胞的Fndc5表达具有依赖于分化的模式，与Pgc-1α表达和肥大平行。鸢尾素以依赖于分化的方式自分泌并显著调节Fndc5和Pgc-1α。肌肉Fndc5表达水平取决于纤维类型和活动类型。
