Palmitic Acid Impairs Myogenesis and Alters Temporal Expression of miR-133a and miR-206 in C2C12 Myoblasts.

Palmitic Acid Impairs Myogenesis and Alters Temporal Expression of miR-133a and miR-206 in C2C12 Myoblasts.
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DOI:
10.3390/ijms22052748
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发表时间:
2021-03-09
影响因子:
5.6
通讯作者:
Rodrigues AC
Rodrigues AC
中科院分区:
生物学2区
文献类型:
--
作者:
da Paixão AO;Bolin AP;Silvestre JG;Rodrigues AC

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棕榈酸(PA)是一种富含高脂饮食的饱和脂肪酸,与肌肉减少性肥胖的发生有关。在此,我们选择了两种非细胞毒性浓度以更好地理解过量的PA如何影响肌管形成或直径而不诱导细胞死亡。48小时的100 µM PA诱导肌管直径减小,I型纤维数量增加,这与miR-206表达增加相关。接下来,评估在PA存在下的C2 C12肌管生长。与对照细胞相比,150 µM PA降低了成肌细胞增殖以及MyoD和miR-206和miR-133 a的表达,导致肌管数量和直径减少。PA(100 µM)尽管不影响增殖,但通过降低Myf 5和miR-206的表达并减少蛋白质合成来损害肌管形成。有趣的是,100和150 µM PA处理的肌管比对照细胞具有更多的II型纤维。总之,PA对肌管直径、融合和代谢产生负面影响,这可能与肌萎缩侧索硬化相关。通过对PA对骨骼肌产生负面影响的机制提供新的见解,我们的数据可能有助于发现治疗肌肉减少性肥胖的新靶点。
Palmitic acid (PA), a saturated fatty acid enriched in high-fat diet, has been implicated in the development of sarcopenic obesity. Herein, we chose two non-cytotoxic concentrations to better understand how excess PA could impact myotube formation or diameter without inducing cell death. Forty-eight hours of 100 µM PA induced a reduction of myotube diameter and increased the number of type I fibers, which was associated with increased miR-206 expression. Next, C2C12 myotube growth in the presence of PA was evaluated. Compared to control cells, 150 µM PA reduces myoblast proliferation and the expression of MyoD and miR-206 and miR-133a expression, leading to a reduced number and diameter of myotubes. PA (100 µM), despite not affecting proliferation, impairs myotube formation by reducing the expression of Myf5 and miR-206 and decreasing protein synthesis. Interestingly, 100 and 150 µM PA-treated myotubes had a higher number of type II fibers than control cells. In conclusion, PA affects negatively myotube diameter, fusion, and metabolism, which may be related to myomiRs. By providing new insights into the mechanisms by which PA affects negatively skeletal muscle, our data may help in the discovery of new targets to treat sarcopenic obesity.
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