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软脂酸可损害成肌分化,并改变 C2C12 成肌细胞中 miR-133a 和 miR-206 的时间表达。

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

机构信息

Department of Pharmacology, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo 05508-000, Brazil.

Department of Anatomy, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo 05508-000, Brazil.

出版信息

Int J Mol Sci. 2021 Mar 9;22(5):2748. doi: 10.3390/ijms22052748.

Abstract

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 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.

摘要

软脂酸(PA)是一种富含高脂肪饮食的饱和脂肪酸,与肌肉减少性肥胖的发展有关。在此,我们选择了两个非细胞毒性浓度,以更好地了解过量的 PA 如何在不诱导细胞死亡的情况下影响肌管形成或直径。100µM PA 作用 48 小时会导致肌管直径减小,并增加 I 型纤维的数量,这与 miR-206 表达增加有关。接下来,评估了 PA 存在下 C2C12 肌管的生长情况。与对照细胞相比,150µM PA 会降低成肌细胞的增殖能力和 的表达以及 miR-206 和 miR-133a 的表达,导致肌管数量和直径减小。PA(100µM)尽管不影响增殖,但通过降低 Myf5 和 miR-206 的表达以及减少蛋白质合成来损害肌管形成。有趣的是,100 和 150µM PA 处理的肌管比对照细胞有更多的 II 型纤维。总之,PA 会负性影响肌管直径、融合和代谢,这可能与肌微小 RNA(miRs)有关。通过提供有关 PA 如何负性影响骨骼肌的机制的新见解,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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe8b/7963199/030a1028d444/ijms-22-02748-g001.jpg

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