Increased Expression of Syncytin-1 in Skeletal Muscle of Humans With Increased Body Mass Index.

Increased Expression of Syncytin-1 in Skeletal Muscle of Humans With Increased Body Mass Index.
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DOI:
10.3389/fphys.2022.858341
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发表时间:
2022
影响因子:
4
通讯作者:
--
中科院分区:
医学2区
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--
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肥胖对骨骼肌蛋白质代谢产生负面影响,也损害骨骼肌的维持和再生。我们分析了来自体重指数(BMI)增加(即> 30 kg/m2)的人和对照(即,BMI < 25 kg/m2)用于表达合胞素-1,一种调节骨骼肌再生的融合蛋白。当与对照相比时,具有增加的BMI和伴随的肌肉蛋白质合成减少的人在骨骼肌中具有更高的合胞素-1表达(p < 0.05)。在人类受试者中,肌肉蛋白质合成与肌肉中的合胞素-1表达呈负相关(r =-0.51; p = 0.03)。使用C2 C12细胞系,我们发现合胞素-A(即,鼠组织中的相应蛋白质)的表达被胰岛素增加,并且这种反应在脂肪酸存在下受损,脂肪酸的代谢在由增加的BMI诱导的代谢环境内改变。在C2 C12细胞中,蛋白质4 E-BP 1的反应类似于合胞素-A的反应,该蛋白质4 E-BP 1信号增加肌肉中的蛋白质合成。这些发现提供了新的见解合胞素-1的表达在骨骼肌的人增加BMI,以及其基本的调节胰岛素和脂肪酸在肌肉中。这些发现表明,需要进一步研究BMI增加的人骨骼肌中合胞素-1的调节,以及其改变肌肉蛋白质代谢和再生的生物学意义。
Obesity negatively impacts skeletal muscle protein metabolism, and also impairs skeletal muscle maintenance and regeneration. We analyzed muscle biopsy samples from humans with increased body mass index (BMI) (i.e. > 30 kg/m2) and controls (i.e., BMI < 25 kg/m2) for expression of syncytin-1, a fusogenic protein regulating skeletal muscle regeneration. When compared to controls, humans with increased BMI and concomitant reduction in muscle protein synthesis had higher expression of syncytin-1 in skeletal muscle (p < 0.05). Across human subjects, muscle protein synthesis correlated inversely (r = −0.51; p = 0.03) with syncytin-1 expression in muscle. Using a C2C12 cell line we found that expression of syncytin-A (i.e, corresponding protein in murine tissue) is increased by insulin, and that this response is impaired in the presence of fatty acids, whose metabolism is altered within the metabolic environment induced by increased BMI. In C2C12 cells, the response of the protein 4E-BP1, which signals increase in protein synthesis in muscle, resembled that of syncytin-A. These findings provide novel insights into the expression of syncytin-1 in skeletal muscle of humans with increased BMI, as well as its basic regulation by insulin and fatty acids in muscle. The findings signify the need for further research into the regulation of syncytin-1 in skeletal muscle of humans with increased BMI, as well as its biological implications for altering muscle protein metabolism and regeneration.
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